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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 145 records · Page 8Linked to original sources
PubMed2000

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience.

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.

Aged↗
PubMed2000

Structural comparison of the PhoB and OmpR DNA-binding/transactivation domains and the arrangement of PhoB molecules on the phosphate box.

PhoB is a transcriptional activator that binds to the phosphate box in the promoters of the phosphate genes of Escherichia coli. PhoB contains two functional domains, an N-terminal phosphorylation domain and a C-terminal DNA-binding/transactivation domain. Here, the three-dimensional structure of the DNA-binding/transactivation domain has been determined by NMR. It consists of an N-terminal four-stranded beta-sheet, a central three helical bundle and a C-terminal beta-hairpin. The second and third helices form a helix-turn-helix (HTH) variant containing a longer turn than the corresponding turn of the classical HTH motif. The overall architecture is very close to that of the OmpR DNA-binding/transactivation domain, however, the conformation of the long turn region of PhoB, a putative interaction site for the RNA polymerase sigma subunit, is entirely different from that of the corresponding turn of OmpR, which interacts with the alpha subunit. In addition, the third helix of PhoB is three amino acid residues longer than the corresponding helix of OmpR. The binding site of PhoB is a TGTCA sequence and the phospahte box contains the two binding sites. NMR studies of the complexes of the PhoB DNA-binding/transactivation domain bound to several different DNA molecules have revealed that two PhoB molecules bind in a tandem array on the phosphate box. In each complex of PhoB the third helix of the DNA-binding/transactivation domain is likely to recognize the TGTCA sequence from the major groove of DNA and the C-terminal beta-hairpin contacts on the minor groove of the 3' site out of the TGTCA sequence in a non-specific manner. The long turn region facing outward is likely to interact with the sigma subunit.

Amino Acid Sequence↗
PubMed2000

Flexible synthesis and biological activity of uronic acid-type gem-diamine 1-N-iminosugars: a new family of glycosidase inhibitors.

An efficient and flexible synthetic route to four gem-diamine 1-N-iminosugars of uronic acid-type (D-glucuronic, D-mannuronic, L-iduronic, and L-guluronic acid), a new family of glycosidase inhibitor, from l-galactono-1,4-lactone have been developed in an enantiodivergent fashion through a sequence involving as the key steps (a) the formation of gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal and (b) the introduction of a carboxylic acid group by the Wittig reaction of a ketone, hydroboration and oxidation, and the Sharpless oxidation. D-Glucuronic and D-mannuronic acid-type 1-N-iminosugars, (3S,4R,5R, 6R)- and (3S,4R,5R,6S)-4, 5-dihydroxy-6-trifluoroacetamido-3-piperidinecarboxylic acid, were proven to be potent inhibitors for beta-D-glucuronidase (IC(50) 6.5 x 10(-)(8)M) and to affect human heparanase (endo-beta-glucuronidase).

Animals↗
PubMed2000

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PURPOSE: The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. METHODS AND MATERIALS: Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. RESULTS: In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. CONCLUSION: Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Adult↗
PubMed2000

Analysis of HLA-DRB1 alleles in Japanese patients with chronic myelogenous leukemia.

To clarify the association between HLA-DRB1 alleles and chronic myelogenous leukemia (CML), the HLA-DRB1 allele frequencies in 50 Japanese patients each with b2a2 and b3a2 CML and 127 healthy Japanese individuals were examined. In the patients with b2a2 CML, the frequencies of HLA-DRB1*0405, DRB1*08032, and DRB1*1502 were low and that of HLA-DRB1*1201 was high in comparison with the healthy individuals. The frequencies of HLA-DRB1*0403, DRB1*0802, DRB1*1403, and DRB1*1405 were high, and those of HLA-DRB1*08032 and DRB1*1501 were low in the patients with b3a2 CML. The present results suggest positive and negative associations between certain HLA-DRB1 alleles and CML.

Alleles↗
PubMed2000

Energy-gap dependence of photoinduced charge separation and subsequent charge recombination in 1,4-phenylene-bridged zinc--free-base hybrid porphyrins

A series of 1,4-phenylene-bridged ZP-HP hybrid porphyrins (ZP = zinc porphyrin, HP = free-base porphyrin) 1-8 ZH have been prepared in which an electron-donating ZP moiety is kept constant and electron-accepting HP moieties are varied by introducing electron-accepting substituents, so that the energy gap for charge separation, ZP-1HP*--> ZP(+)-HP-, covers a range of about 0.9 eV in DMF. Here selective excitation at the HP moiety was employed to avoid complication in the determination of electron transfer rates derived from energy transfer, 1ZP*-HP --> ZP-1HP*. Definitive evidence for the electron transfer has been obtained in three solvents (benzene, THF, and DMF) through picosecond-femtosecond transient absorption studies, which have allowed the determination of the rates of the photoinduced charge separation, ZP-1HP* --> ZP(+)-HP-, and subsequent thermal charge recombination ZP(+)-HP- --> ZP-HP. Dyad 1ZH in THF exhibits a biphasic fluorescence decay that indicates thermal repopulation of the ZP-1HP* from ZP(+)-HP-; this has been also supported by the transient absorption spectra. On this ground, the energy levels of the ZP(+)-HP- ion pairs have been estimated. Similar biphasic fluorescence decay has been observed for 5 ZH in benzene; this allows furhter estimation of the energy level of the ZP(+)-HP- ion pairs. The free-energy-gap dependence (energy-gap law) has been probed from the normal to the upper limit region for the rate of the charge separation alone, and only the inverted region for the rate of the charge recombination. It was not possible to reproduce both energy-gap dependencies of the charge separation and the charge recombination assuming common parameter values for the reorganization energy and electronic interaction responsible for the electron transfer with the classical Marcus equation. Although both energy-gap dependencies can be approximately reproduced by means of the simplified semiclassical equation, which takes into consideration the effect of the high-frequency vibrations replaced by one mode of averaged frequency, many features, which include the effects of solvent polarity, electron-tunneling matrix element, and so forth on the energy-gap law, are considerably different from those of the previous studied porphyrin-quinone systems with weaker inter-chromophore electronic interactions.

Journal Article↗
PubMed2000

Small guanosine triphosphatase Rho/Rho-associated kinase as a novel regulator of intracellular redistribution of lysosomes in invasive tumor cells.

To investigate the role of RhoA on the intracellular membrane dynamics of lysosomes in rat hepatoma cells (MM1), we analyzed the localization of lysosomal aspartic proteinase cathepsin D by confocal immunofluorescence microscopy in the dominant active RhoA-transfected cells. Here we show that the transfection of the dominant active form of human small guanosine triphosphatase (GTPase) RhoA in MMI cells, a highly invasive cell line, causes the redistribution and spreading of small punctate structures stained for cathepsin D throughout the cytoplasm. We found that the microtubule organization was markedly different in the two cell lines: uniformly developed and polymerized microtubule filaments were seen in the mock transfectants; however, the dynamic organization of microtubules was less pronounced in the active RhoA transfectants. Furthermore, we found for the first time that a selective inhibitor of Rho-associated kinase (p160ROCK), Y-27632, impeded the subcellular spreading of cathepsin D staining and promoted reclustering of cathepsin D toward the perinuclear region in the active RhoA-transfected cells. To our knowledge, this is the first indication that the RhoA/ROCK-mediated signaling pathway is involved in the intracellular membrane dynamics of lysosomes by regulating the cytoskeletal microtubule organization as well as the actin cytoskeletons.

Actins↗
PubMed2000

Ascending versus descending aortic balloon pumping: organ and myocardial perfusion during ischemia.

BACKGROUND: The ICS-Supracor (Abiomed, Danvers, MA) is a preshaped ascending aorta balloon pump. We compared the effects of this catheter with the classical descending intraaortic balloon pump (IABP). The study focused on hemodynamic effects, myocardial blood flow in normal and ischemic regions, cerebral perfusion, and peripheral organ perfusion. METHODS: We placed a stenosis on the lateral branch of the coronary artery to reduce flow 50% (sheep). Measurements included hemodynamic changes, myocardial blood flow, and organ flow (colored microspheres) at baseline, after stenosis, during IABP support, and during ICS support. RESULTS: Counterpulsation with the ICS led to a significantly higher peak diastolic aortic augmentation than with the IABP (IABP, 99 +/- 14 mm Hg; ICS, 140 +/- 29 mm Hg; p = 0.003). There was no significant change in cerebral perfusion or peripheral organ perfusion. Myocardial blood perfusion was significantly increased by the IABP as well as the ICS. This effect was seen in ischemic and nonischemic regions (subendocardial and subepicardial). The ICS improved myocardial blood flow significantly more than the IABP (IABP, 0.65 +/- 0.1 mL/min/g; ICS, 0.94 +/- 0.06 mL/min/g; p = 0.0005). CONCLUSIONS: The ICS increases myocardial blood flow in ischemic regions significantly more than the IABP, without impairment of cerebral flow. Assessment of vascular complications, peripherally and in the ascending aorta, has to await results of clinical trials.

Animals↗
PubMed2000

Accelerated tissue regeneration through incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis.

The objective of this study was to evaluate the effect of incorporation of basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres into an artificial dermis on the regeneration of dermis-like tissues. When used in the free form in vivo, bFGF cannot induce sufficient wound healing activity, because of its short half-life. Therefore, sustained release of bFGF was achieved by impregnation into biodegradable gelatin microspheres. A radioisotope study revealed that incorporation of bFGF-impregnated gelatin microspheres significantly prolonged in vivo retention of bFGF in the artificial dermis. Artificial dermis with incorporated bFGF-impregnated gelatin microspheres or bFGF in solution was implanted into full-thickness skin defects on the back of guinea pigs (1.5 cm x 1.5 cm) (n = 4). Incorporation of bFGF into the artificial dermis accelerated fibroblast proliferation and capillary formation in a dose-dependent manner. However, the accelerated effects were more significant with the incorporation of bFGF-impregnated gelatin microspheres than with free bFGF at doses of 50 microg or higher. We conclude that the gelatin microsphere is a promising tool to accelerate bFGF-induced tissue regeneration in artificial dermis.

Animals↗
PubMed2000

Efficient expression of the envelope protein of feline immunodeficiency virus in a recombinant feline herpesvirus type 1 (FHV-1) using the gC promoter of FHV-1.

We constructed two recombinant feline herpesvirus type 1 (FHV-1) expressing the envelope (Env) protein of feline immunodeficiency virus (FIV). One recombinant, designated dlTK-env, has the whole FIV env gene inserted at a thymidine kinase (TK) deletion site. The second recombinant, designated dlTK(gCp)-env, has a cassette containing a partial FIV env gene fused with the signal sequence of the gC protein of FHV-1 (under the control of the gC promoter) inserted at the same site. Growth kinetics of both the recombinants in Crandell feline kidney (CRFK) cells were similar to that of the parent strain of FHV-1. By indirect immunofluorescence assays and immunoblot analyses, we confirmed the expression of the FIV Env protein in CRFK cells infected with both recombinants. Enzyme-linked immunosorbent assays showed that the maximum Env expression level achieved by dlTK(gCp)-env was more than four times higher than that observed for dlTK-env. Flow cytometric analyses revealed that the Env protein produced by both recombinants was efficiently expressed on the cell surface. The dlTK(gCp)-env reported here may thus be a promising candidate for a live recombinant vaccine to protect against FIV infection.

Animals↗
PubMed2000

Analysis of T cell responses to the beta 2-glycoprotein I-derived peptide library in patients with anti-beta 2-glycoprotein I antibody-associated autoimmunity.

Antiphospholipid syndrome (APS) is an autoimmune disease that accompanies anti-phospholipid antibodies measured as either anti-cardiolipin antibodies (aCL) or lupus anticoagulant. beta(2)-glycoprotein I (beta(2)GPI) is the most common and apparently the best-characterized antigenic target for aCL. To investigate T-cell responses to beta(2)GPI, we stimulated PBMC of 18 APS or systemic lupus erythematosus (SLE) patients carrying anti-beta(2)GPI and 10 healthy controls, using a peptide library covering the beta(2)GPI sequence. We established seven CD4(+) T cell lines reactive with beta(2)GPI peptide. Three of four epitopes for patient-derived T cell lines were p244-264, whereas one T cell line from a control subject also recognized p244-264. Furthermore, there was no tendency for particular HLA class II molecules to present beta(2)GPI peptides. However, cytokine producing patterns were significantly different between T cell lines from patients and those from healthy individuals (p =.028); patients' T cells tend to exhibit higher IL-4 and lower IFN-gamma responses. These T cell lines did not react to beta(2)GPI purified from human plasma. These results indicate that beta(2)GPI-reactive CD4(+) T cells of APS/SLE patients mainly recognize cryptic p244-264 in the context of various HLA class II molecules, and exhibit Th0-Th2-type responses. Our findings may provide a clue to the pathogenesis of APS.

Adult↗
PubMed2000

Persistent hypoglossal artery associated with arteriovenous malformation: a case report.

A rare case of persistent hypoglossal artery in conjunction with arteriovenous malformation was presented. MRA could delineate persistent hypoglossal artery and arteriovenous malformation very clearly. The patient suffered from intracranial hemorrhage from in the 37th week of pregnancy. MRI, MRA, angiography, and CT of this rare condition are reported.

Adult↗
PubMed2000

A case of Marchiafava-Bignami disease: MRI findings on spin-echo and fluid attenuated inversion recovery (FLAIR) images.

Marchiafava-Bignami disease (MBD) was diagnosed in a 56-year-old man. Spin-echo (SE) magnetic resonance imaging (MRI) at the acute phase showed normal signal areas in the central layer of the corpus callosum (CC), although the intensity of these areas revealed abnormal hyperintensity on fluid attenuated inversion recovery (FLAIR). On follow-up SE MRI at the late phase, the central layer of the CC showed fluid-like intensity. On FLAIR MRI, the lesions of the CC turned into hypointense cores surrounded by hyperintense rims indicating central necrosis and peripheral demyelination. Degenerative changes of the CC in MBD were clearly demonstrated by FLAIR MRI.

Alcoholism↗
PubMed2000

gem-diamine 1-N-iminosugars of L-fucose-type, the extremely potent L-fucosidase inhibitors.

An efficient route from D-ribono-gamma-lactone to gem-diamine 1-N-iminosugars of L-fucose-type, a new family of glycosidase inhibitor, has been developed in a formation of a gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal as a key step. The analogues were proved to be the extremely potent inhibitors against alpha-L-fucosidase (IC50 approximately 3 ng mL(-1), Ki approximately 5 x 10(-9) M). The present study has shown that a cyclic methanediamine generated in media affects glycosidases as a real active-form of the gem-diamine 1-N-iminosugars of L-fucose-type.

Carbohydrate Sequence↗
PubMed2000

Both the HLA-CPB1 and -DRB1 alleles correlate with risk for multiple sclerosis in Japanese: clinical phenotypes and gender as important factors.

The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with multiple sclerosis (MS) in Japanese, to determine whether optico-spinal MS (OS-MS) and conventional MS are immunogenetically distinct, and to verify the role of gender difference in HLA associations of MS. We studied HLA-DRB1 and -DPB1 polymorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the optico-spinal MS (OS-MS) and 119 as having conventional MS. A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS. By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28). Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS. However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients. We did not find any association of these HLA alleles with disease course and severity. In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.

Alleles↗
PubMed2000

Structural genomics projects in Japan.

Two major structural genomics projects exist in Japan. The oldest, the RIKEN Structural Genomics Initiative, has two major goals: to determine bacterial, mammalian, and plant protein structures by X-ray crystallography and NMR spectroscopy and to perform functional analyses with the target proteins. The newest, the structural genomics project at the Biological Information Research Center, focuses on human membrane proteins.

Animals↗