Search PubMed⌕ Search

Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 127 records · Page 7Linked to original sources
PubMed2000

Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer.

PURPOSE: To determine the survival of pancreatic cancer patients treated with intraoperative radiotherapy (IORT) and/or external beam radiation therapy (EBRT) following macroscopically curative resection. METHODS AND MATERIALS: One hundred and thirty-eight patients with pancreatic cancer who had undergone potentially curative total or regional pancreatectomy between 1980 and 1997 were retrospectively analyzed. Among the 138 patients, 98 had a pathologically negative surgical margin and the remaining 40 patients had a positive surgical margin. The usual EBRT dose was 45-55 Gy with a daily fraction of 1.5-2.0 Gy. The median IORT dose was 25 Gy in a single fraction. RESULTS: The 2-year cause-specific survival rate of patients with pathologically negative surgical margins was 19%, and that of patients with positive margins was 4% (p < 0.005). Although the median survival time (MST) of patients with negative margins treated with IORT and EBRT was significantly longer than that of those treated with operation alone (17 vs. 11 months), no significant difference in survival curves was observed. In patients with positive surgical margins in peripancreatic soft tissue, the difference between the survival curve of patients treated with surgery alone and that of those treated with surgery and radiation therapy was borderline significant (p < 0.10). Patients receiving intraarterial or intraportal infusion chemotherapy had significantly improved survival rates compared with those who did not receive it (p < 0.05). CONCLUSION: Although the MST was longer in patients with negative margins receiving IORT and EBRT than in those receiving no radiation, improved long-term survival by IORT and/or EBRT was not suggested. In patients with positive margins, our results obtained by IORT/EBRT were encouraging. Randomized studies with much higher patient numbers are necessary to define the role of IORT in curatively resected pancreatic cancer.

Adult↗
PubMed2000

A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation.

The authors report a patient carrying a missense mutation in exon 10 of tau that causes a substitution at codon 301 (P301S). Although the patient shares the rapidly progressive frontotemporal dementia of the other reported pedigrees with P301S, the clinical phenotype is unique in that parkinsonism was a major symptom in the early stage and because behavioral symptoms with dementia became prominent 2 years after the onset of the disease. This study substantiates the notion that tau mutations at codon 301 can show various phenotypes.

Adult↗
PubMed2000

Three-dimensionally arranged windmill and grid porphyrin arrays by AgI-promoted meso-meso block oligomerization

The syntheses of soluble windmill and grid porphyrin arrays through the AgI-promoted coupling reaction of 1,4-phenylene-bridged linear porphyrin arrays, which are comprised of a central ZnII beta-free porphyrin and flanking peripheral NiII beta-octaalkylporphyrins, are described. The coupling reaction is advantageous in light of its high regioselectivity occurring only at the meso-position of the ZnII beta-free porphyrin as well as its easy extension to large porphyrin arrays. The windmill porphyrin arrays in turn serve as an effective substrate for further coupling reactions, to give three-dimensionally arranged grid porphyrin arrays. Further the grid porphyrin 12-mer (a tetramer of the linear porphyrin trimer) was also coupled to afford grid porphyrins (24-mer, 36-mer, and 48-mer). These porphyrin arrays were isolated in a discrete form by repetitive GPC/HPLC (GPC= gel-permiation chromatography). Competitive experiments with three linear porphyrin trimers bearing different peripheral metalloporphyrins (ZnII, NiII, and Cull), and the trapping experiment of the radical cation at the peripheral porphyrin with AgNO2, suggested that an initial one-electron oxidation of the easily oxidizable peripheral ZnII beta-octaalkylporphyrin with an AgI ion and a subsequent endothermic hole transfer assist the generation of the radical cation at the central ZnII beta-free porphyrin. In all ZnII-metallated windmill porphyrin arrays, the energy level of the S1 state of the meso-meso-linked diporphyrin core is lower than that of the peripheral porphyrins, thereby allowing an energy flow from the peripheral porphyrins to the central diporphyrin core; this has been confirmed by measurements of fluorescence lifetimes and picosecond time-resolved fluorescence spectra. The excitation energy transfer in the arrays encourages their potential use as an light-harvesting antenna.

Journal Article↗
PubMed2000

All eight stereoisomeric D-glyconic-delta-lactams: synthesis, conformational analysis, and evaluation as glycosidase inhibitors.

An efficient and general synthetic route to all eight stereoisomeric D-glycono-delta-lactams has been developed. The strategy involves, as a key step, a stereodivergent delta-lactam formation with configurational retention or inversion at C-4 of a starting gamma-lactone to lead to two epimers of delta-lactam from one parent gamma-lactone. Conformations of eight glycono-delta-lactams were examined by X-ray crystallographic analysis and molecular modeling. Analyses of conformation and glycosidase-inhibition provide useful information for the design of new glycosidase inhibitors.

Animals↗
PubMed2000

Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by an intrahepatic inoculation with an expression plasmid.

We assessed the possibility of intrahepatic inoculation with a plasmid encoding hepatitis C virus (HCV) proteins to elicit HCV-specific cytotoxic T lymphocytes (CTL) in mice as a conventional animal model of HCV infection. BALB/c mice were intrahepatically or intramuscularly inoculated with an expression plasmid DNA encoding HCV structural proteins under the control of the elongation factor 1-alpha promoter. Expressions of HCV-core protein and envelope proteins (E1 and E2) in hepatocytes were detected immunohistochemically 6 days after inoculation. CTL responses were examined using target cells either pulsed with a specific peptide or infected with a recombinant vaccinia virus expressing HCV structural protein. Both intrahepatically and intramuscularly DNA-inoculated mice developed CD8(+), MHC class I-restricted CTL responses that recognized the peptide pulsed as well as HCV proteins expressing target cells. These studies demonstrated the usefulness of a murine model of HCV infection induced by direct intrahepatic DNA inoculation for understanding the immunopathogenic mechanisms in HCV infection.

Animals↗
PubMed2000

Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells.

Ceramide has recently been regarded as a potential mediator of apoptosis. In the present study, the effects of Bcl-2 and Bax on the ceramide-mediated apoptotic pathways were examined in glioma cells overexpressing Bcl-2 or Bax. Etoposide, cisplatin and tumor necrosis factor-alpha induced apoptosis of C6 rat glioma cells which was associated with ceramide formation due to activation of neutral sphingomyelinase, followed by release of mitochondrial cytochrome c into the cytosol and activation of caspases-9 and -3. The growth of C6 cells stably overexpressing either Bcl-2 or Bax was almost equal to that of the vector-transfected cells. Bax overexpression enhanced etoposide-induced apoptosis through acceleration of cytochrome c release and caspases activation. However, Bax had no effect on ceramide formation. Similar findings were obtained in C6 cells and U87-MG human glioblastoma cells which were transiently overexpressed with Bax. In contrast, Bcl-2 overexpression resulted in a retardation of the apoptotic process via prevention of cytochrome c release and caspases activation, and ceramide formation was also blocked when Bcl-2 was highly overexpressed in glioma cells. In addition, transient overexpression of Bcl-xL also exerted inhibitory effects on ceramide formation and apoptotic cell death induced by etoposide. These results indicate that Bax promotes apoptosis regardless of ceramide formation and that Bcl-2 or Bcl-xL prevents ceramide formation by repressing neutral sphingomyelinase as well as ceramide-induced cytochrome c release. Oncogene (2000) 19, 3508 - 3520

Animals↗
PubMed2000

Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist candesartan blocks brain AT(1) receptors.

Brain Angiotensin II, through stimulation of brain AT(1) receptors, regulates pituitary hormones and autonomic activity. We have administered the insurmountable AT(1) antagonist Candesartan, s.c. via osmotic minipumps for 14 days, to determine whether peripheral chronic AT(1) blockade affects AT(1) receptor binding and mRNA in the brain. Peripherally administered Candesartan (0.1, 0.5 or 1.0 mg/kg per day) inhibits AT(1) binding in adrenal gland zona glomerulosa and kidney glomeruli. In addition, Candesartan dose-dependently decreases AT(1) binding in brain areas outside (subfornical organ and area postrema) and inside (paraventricular nucleus of the hypothalamus and nucleus of the solitary tract) the blood-brain barrier. Conversely, peripheral treatment with Candesartan does not affect AT(1A) receptor mRNA, the predominant receptor subtype expressed in these areas, or Angiotensin II binding to AT(2) receptors in the locus coeruleus or inferior olive. Our results demonstrate that chronic peripheral treatment with selective, potent AT(1) antagonists not only inhibits peripheral but also brain AT(1) receptors. These central effects may play a role in the antihypertensive effects of the AT(1) antagonist Candesartan.

Angiotensin Receptor Antagonists↗
PubMed2000

An amiloride-sensitive and voltage-dependent Na+ channel in an HLA-DR-restricted human T cell clone.

We investigated changes in voltage-gated Na+ currents and effects of extracellular Na+ on proliferation in HLA-DR-restricted human CD4+ alphabeta T cells after stimulation with a non-self antigenic peptide, M12p54-68. In the absence of antigenic peptide, neither single (n = 80) nor APC-contacted (n = 71) T cells showed voltage-gated inward currents recording with whole-cell patch-clamp techniques, even with Ca2+ and Na+ ions present in the perfusion solution. However, with the same recording conditions, 31% (26 of 84) of APC-contacted T cells stimulated with the antigenic peptide showed voltage-dependent inward currents that were elicited from -60 mV. The inward currents were not inhibited in extracellular Ca2+-free conditions or in the presence of 1 mM NiCl2. However, they were completely inhibited in extracellular Na+-free conditions, which were made by replacing Na+ with iso-osmotic N-methyl-d -glucamine or choline. The Na+ currents were insensitive to tetrodotoxin, a classical blocker of Na+ channels, but were dose-dependently inhibited by amiloride, a potassium-sparing pyrazine diuretic. Furthermore, the Ag-specific proliferative response of T cells was completely inhibited in Na+-free Tyrode's solution and was suppressed by amiloride in a dose-dependent manner. Our findings suggest that activation of amiloride-sensitive and voltage-gated Na+ channels would be an important step to allow an adequate influx of Na+ and maintain a sustained high Ca2+ level during T cell activation.

Amiloride↗
PubMed2000

Activity-dependent slow hyperpolarization in cat sensorimotor cortex in vitro.

The synaptic regulatory mechanism of resting membrane potential of layer III and V pyramidal neurons was analyzed intracellularly in the slice preparation of cat sensorimotor cortex. During the tetanic stimulation of white matter, subthreshold membrane depolarization was induced, and after that, a slowly developing hyperpolarization was induced in the normal solution. When the membrane potential showed a slow change, spike duration and input resistance did not change and evoked single synaptic response did not reveal the enhancement of slow IPSPs. However, afterhyperpolarization following action potential was enhanced. The slow hyperpolarization and the enhancement of afterhyperpolarization were not observed in the cells treated with an NMDA receptor antagonist or a calcium channel blocker Ni(2+) (50-100 microM), or the cells hyperpolarized more than -80 mV before the tetanic stimulation.

Action Potentials↗
PubMed2000

Mouse and human GTPBP2, newly identified members of the GP-1 family of GTPase.

We earlier identified the GTPBP1 gene which encodes a putative GTPase structurally related to peptidyl elongation factors. This finding was the result of a search for genes, the expression of which is induced by interferon-gamma in a macrophage cell line, THP-1. In the current study, we probed the expressed sequence tag database with the deduced amino acid sequence of GTPBP1 to search for partial cDNA clones homologous to GTPBP1. We used one of the partial cDNA clones to screen a mouse brain cDNA library and identified a novel gene, mouse GTPBP2, encoding a protein consisting of 582 amino acids and carrying GTP-binding motifs. The deduced amino acid sequence of mouse GTPBP2 revealed 44.2% similarity to mouse GTPBP1. We also cloned a human homologue of this gene from a cDNA library of the human T cell line, Jurkat. GTPBP2 protein was found highly conserved between human and mouse (over 99% identical), thereby suggesting a fundamental role of this molecule across species. On Northern blot analysis of various mouse tissues, GTPBP2 mRNA was detected in brain, thymus, kidney and skeletal muscle, but was scarce in liver. Level of expression of GTPBP2 mRNA was enhanced by interferon-gamma in THP-1 cells, HeLa cells, and thioglycollate-elicited mouse peritoneal macrophages. In addition, we determined the chromosomal localization of GTPBP1 and GTPBP2 genes in human and mouse. The GTPBP1 gene was mapped to mouse chromosome 15, region E3, and human chromosome 22q12-13.1, while the GTPBP2 gene is located in mouse chromosome 17, region C-D, and human chromosome 6p21-12.

Amino Acid Sequence↗
PubMed2000

Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinduction in vivo.

Bone morphogenetic proteins (BMP) are unique molecules with a specific biological activity for inducing ectopic bone formation when implanted with a suitable carrier matrix. However, incorporation of BMP into the carrier has disadvantages, including early burst release and protein degradation in biological environments. Therefore, we considered that the next greatest challenge in achieving successful clinical use was the development of a carrier system for site-specific delivery of the morphogenetic signal of BMP. In this study, a novel BMP-2-derived oligopeptide, NSVNSKIPKACCVPTELSAI, was coupled covalently to alginate. Then NSVNSKIPKACCVPTELSAI-linked alginate hydrogel composites were implanted into the calf muscle of rats and harvested 3 or 8 weeks after surgery. Ectopic bone formation was observed in alginate hydrogel linked with BMP-2-derived peptide. It is suggested that alginate hydrogel linked with an oligopeptide derived from BMP-2 might provide an alternative system for topical delivery of the morphogenetic signal of BMP-2.

Amino Acid Sequence↗
PubMed2000

Combined effects of tirapazamine and mild hyperthermia on anti-angiogenic agent (TNP-470) treated tumors-reference to the effect on intratumor quiescent cells.

PURPOSE: To evaluate the efficacy of the use of tirapazamine (TPZ), especially combined with mild hyperthermia (40 degrees C, 60 min), in the treatment of solid tumors following an anti-angiogenic treatment with TNP-470. In addition, we assessed the effect of TPZ and/or mild hyperthermia (MHT) combined with conventional radiotherapy or chemotherapy on TNP-470 treated tumors. MATERIALS AND METHODS: C3H/He mice bearing SCC VII tumors subcutaneously received TNP-470 at two doses of 100 mg/kg after tumor cell inoculation. At the same time, the tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received TPZ administration combined with or without MHT, gamma-ray irradiation combined with or without TPZ and/or MHT, or cisplatin injection with or without TPZ and/or MHT. Another group of mice received a series of test doses of gamma-rays while alive or after being killed to obtain hypoxic fractions (HFs) in the tumors at various time points after the above-mentioned cytotoxic treatment point. After each treatment, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (or quiescent [Q] cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN frequency of BrdU-unlabeled cells was then used to calculate the surviving fraction of the unlabeled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total tumor cells. RESULTS: TPZ administration combined with TNP-470 treatment and MHT increased the MN frequency more markedly than treatment with TPZ alone, and this tendency was more remarkable in Q cells than total cells. In both total and Q cells, combined treatment with TPZ and MHT produced significant increases in MN frequencies whether gamma-rays were delivered to TNP-470 treated tumors or cisplatin was injected into the TNP-470 administered mice. Although not significantly, the HFs of total and Q cell populations within solid tumors increased after TNP-470 treatment. CONCLUSION: Combined treatment with TPZ and MHT, whether other cytotoxic treatments such as gamma-ray irradiation or chemotherapy using cisplatin were combined or not, was useful for sensitizing tumor cells in vivo including Q cells even after TNP-470 treatment.

Angiogenesis Inhibitors↗
PubMed2000

Inhibitory effect of stromal cell derived factor-1 on the replication of divergent strains of feline immunodeficiency virus in a feline T-lymphoid cell line.

The effect of a CXC-chemokine, stromal cell derived factor-1 (SDF-1), on the replication of divergent strains of feline immunodeficiency virus (FIV) was examined in order to identify the mechanism of cell entry of FIV. A chemotaxis assay, using a modified Boyden chamber method, confirmed the biological activity of recombinant human (rh) SDF-1 for a feline T-lymphoid cell line (Kumi-1). The viral replication of FIV, as measured by the reverse transcriptase (RT) activity in the culture supernatant, was significantly suppressed by addition of rhSDF-1 in a dose-dependent manner in Kumi-1 cells. Furthermore, PCR analysis of the FIV proviral genome indicated that the inhibitory effect of rhSDF-1 on the replication of FIV in Kumi-1 cells was due to the inhibitory effect in the early event of replication. The inhibitory effect on viral replication by exogenous rhSDF-1 was shown for four divergent FIV isolates of subtypes A, B, and D in Kumi-1 cells.

Animals↗
PubMed2000

Tumor necrosis factor-alpha augments contraction and cytosolic Ca(2+) sensitivity through phospholipase A(2) in bovine tracheal smooth muscle.

To elucidate the effects of tumor necrosis factor-alpha (TNF-alpha) on tracheal smooth muscle contraction, we simultaneously measured isometric tension and intracellular Ca(2+) ([Ca(2+)](i)) in fura 2-loaded muscle strips. Smooth muscle force generation was evaluated in a high potassium (K(+); 20.0-80.0 mM) solution and with acetylcholine (3 nM-10 microM ). TNF-alpha (1-100 ng/ml) did not directly contract muscle strips. The contractile response to acetylcholine was enhanced after application of 10 ng/ml of TNF-alpha for 30 min but not the response of [Ca(2+)](i). The contractile response and the response of [Ca(2+)](i) to a high K(+) solution were not altered after application of TNF-alpha. The [Ca(2+)](i)-tension curve indicated that TNF-alpha enhanced the responsiveness of tracheal smooth muscle through the acetylcholine-mediated Ca(2+) sensitivity of intracellular contractile elements. The augmentation of the acetylcholine concentration-response curves for muscle tension in the presence of TNF-alpha (10 ng/ml) was inhibited in part after application of manoalide, a phospholipase A(2) inhibitor. We conclude that a low concentration of TNF-alpha enhances smooth muscle responsiveness to acetylcholine by agonist-mediated Ca(2+) sensitivity facilitated by phospholipase A(2).

Acetylcholine↗
PubMed2000

Reconstruction of rat peripheral nerve gap without sutures using freeze-dried alginate gel.

Many materials have been used for artificial tubular prostheses to assist peripheral nerve gap reconstruction. However, the clinical use of these devices has been restricted because a microsurgical procedure requires specialized techniques and expensive equipment, such as operating microscope systems. Therefore the authors developed a new gluing method, without sutures, that uses freeze-dried alginate gel. A 7-mm gap in the sciatic nerve of rats was bridged with freeze-dried alginate gel. Regeneration was evaluated by electrophysiologic testing and histologic study. Eighteen weeks after surgery, functional reinnervation of motor and sensory nerves had occurred, as demonstrated by recovery of compound muscle action potentials (CMAP), compound nerve action potentials (CNAP), and somatosensory-evoked potentials (SEP). Histologically, many regenerated nerve fasciculi, including myelinated and unmyelinated fibers, were observed and the implanted alginate gel had disappeared. In conclusion, a gluing technique using alginate gel is a potential alternative to the conventional nerve autograft technique. Advantages include simple application and rapid repair. Freeze-dried alginate gel is a promising material for artificial nerve guides for peripheral nerves and also could be used for repair of disrupted pathways in central nervous tissue that is amorphous and cannot be sutured.

Action Potentials↗
PubMed2000

Molecular cloning and sequencing of the cDNA encoding the feline FcgammaRIIIA (CD16) homologue.

We amplified the cDNA encoding the feline FcgammaRIIIA (CD16) homologue from peripheral blood mononuclear cells by polymerase chain reaction and cloned two forms of FCGR3A cDNA. Sequencing analysis revealed that the open reading frame of feline FCGR3A cDNA consists of 750 or 747 base pairs encoding 250 or 249 amino acid residues, respectively. Comparison of the predicted amino acid sequence of feline FCGR3A cDNA with those of other mammalians' homologues revealed that the extracellular domain has a relatively low homology. However, the cytoplasmic domain contained an 8-amino acid motif, Leu-Phe-Val-Val-Asp-Thr-Gly-Leu, which was considered to interact with an accessory molecule such as the gamma chain of Fc receptors for IgE to form heterodimeric complexes.

Amino Acid Sequence↗
PubMed2000

Structure of the central core domain of TFIIEbeta with a novel double-stranded DNA-binding surface.

Human general transcription factor TFIIE consists of two subunits, TFIIEalpha and TFIIEbeta. Recently, TFIIEbeta has been found to bind to the region where the promoter starts to open to be single-stranded upon transcription initiation by RNA polymerase II. Here, the central core domain of human TFIIEbeta (TFIIEbetac) has been identified by a limited proteolysis. This solution structure has been determined by NMR. It consists of three helices with a beta hairpin at the C-terminus, resembling the winged helix proteins. However, TFIIEbetac shows a novel double-stranded DNA-binding activity where the DNA-binding surface locates on the opposite side to the previously reported winged helix motif by forming a positively charged furrow. A model will be proposed that TFIIE stabilizes the preinitiation complex by binding not only to the general transcription factors together with RNA polymerase II but also to the promoter DNA, where double-stranded DNA starts to open to be single-stranded upon activation of the preinitiation complex.

Amino Acid Sequence↗