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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 91 records · Page 5Linked to original sources
PubMed2001

Coronary artery bypass grafting in patients with dialysis-dependent renal failure.

The aim of this study was to define short- and long-term results of coronary artery bypass grafting (CABG) in dialysis patients. A retrospective review was carried out on 73 consecutive patients dependent on chronic dialysis who underwent CABG. In 63 isolated CABGs, 9 operations were performed under normal beating heart because of severe atherosclerotic changes in the ascending aorta or carotid arteries. The operative mortality (30 days' mortality) was 4.1%, and causes of death were closely related to cardiopulmonary bypass use. In the last 29 operations after introduction of the beating heart bypass, no hospital deaths occurred. The actual survival rates dropped to 45% at 70 months mainly for noncardiac late death. CABG for dialysis patients as undertaken with an acceptable operative risk. Extended application of beating heart bypass to these patients may produce further positive early results.

Adult↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (5)--Six-month repeated oral dose toxicity study and supplement study in rats].

Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.

Administration, Oral↗
PubMed2001

[A case of primary Sjögren's syndrome with acute transverse myelopathy and polyneuropathy as the initial manifestations].

We report a case of primary Sjögren's syndrome with acute transverse myelopathy and polyneuropathy as the initial manifestations. A 72-year-old man developed acute right hemiparesis and his symptoms deteriorated to quadriparesis in four days. A cervical spinal MRI showed an extensive intraparenchymal lesion with high T2-weighted signal intensity, gadolinium enhancement, and cord swelling. An electromyographic study and a sural nerve biopsy showed severe axonal degeneration. The patient complained of thirst and a salivary gland biopsy revealed inflammatory changes, while salivary gland scintigraphy showed diminished secretion. These findings led to a diagnosis of Sjögren's syndrome. Only one case of Sjögren's syndrome with acute transverse myelopathy as the initial manifestation has been reported. In our case, however, polyneuropathy was observed in addition to transverse myelopathy as the initial manifestation. Even if prominent sicca symptoms are absent, all patients with acute transverse myelopathy and polyneuropathy should be carefully examined with considerations of possible presence of Sjögren's syndrome.

Aged↗
PubMed2001

[AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone marrow transplantation and disappearance of TLS/FUS-ERG mRNA].

A 3-year-old boy with poorly prognostic acute megakaryoblastic leukemia (AML M7) showing t(16;21)(p11;q22) karyotype underwent unrelated bone marrow transplantation (U-BMT) during his first hematological remission. The conditioning regimen consisted of BU, VP-16 and L-PAM. Engraftment was smooth, but the patient developed grade I acute GVHD. During hematological remission before U-BMT, the TLS/FUS-ERG chimeric transcript of t(16;21)(p11;q22) was consistently detectable as minimal residual disease (MRD) by RT-PCR. However, after U-BMT it soon became undetectable. There was no detectable MRD until 7 months after U-BMT, but bone marrow relapse occurred 10 months after U-BMT. We consider that U-BMT is a promising treatment for t(16;21)(p11;q22) AML. However, an intensified conditioning regimen or modification of GVHD prophylaxis is needed.

Bone Marrow Transplantation↗
PubMed2001

[A patient of chronic graft-versus-host disease presenting simultaneously with polymyositis and myasthenia gravis].

We report a patient of polymyositis and myasthenia gravis as manifestations of chronic graft-versus-hot disease (GVHD). A 48-year-old man was diagnosed as having chronic myelogenous leukemia at the age of 42 years, and had bone marrow transplantation (BMT) two years after the onset of the disease. Since he suffered from mild liver dysfunction and cutaneous involvement manifesting chronic GVHD, he was placed on prednisolone and cyclophosphamide. As his condition improved, the prednisolone was gradually tapered. Forty-one months after the BMT, the patient developed muscle pain and muscle weakness. A diagnosis of polymyositis was made from muscle biopsy and laboratory findings. An increase in the prednisolone dose was effective but a few weeks later the patient noticed ptosis and recurrence of muscle weakness. A tensilon test and anti-acetylcholine receptor antibody produced positive results, leading to a diagnosis of myasthenia gravis. Only one case of polymyositis and myasthenia gravis as manifestations of chronic GVHD has been reported, and in our patient both symptoms appeared almost at the same time. Although neuromuscular symptoms as a manifestation of chronic GVHD are rare, all patients receiving BMT should be carefully followed up neurologically to detect neuromuscular complications.

Bone Marrow Transplantation↗
PubMed2000

Coordination control of intramolecular electron transfer in boronate-bridged zinc porphyrin-diimide molecules.

Three sets of dyads, in which a zinc-porphyrin (ZP) electron donor is connected to an aromatic diimide electron acceptor,either pyromellitimide (PI) or naphthalene-1,8:4,5-tetracarboxylic acid diimide (NI), via a boronate-ester bridge, a piperidine bridge, and a 1,3-dioxolane bridge, respectively, were prepared for the purpose of control of intramolecular electron transfer (ET) by acid-base reactions at the connecting bridge. Boronate-ester bridge is a Lewis acidic site and confers a chance to regulate intramolecular ET reaction upon base coordination. This has been demonstrated by suppression of photoinduced ET from ZP to PI or NI in highly electron-pair donating solvents or upon addition of a fluoride anion. To extend this strategy to control of ET-path selectivity, we prepared triad 18, which consists of a ZP donor bearing NI and PI acceptors at similar distances through a boronate-ester bridge and an acetal bridge, respectively. Photoexcitation of 18 in a free form led to intramolecular ET from (1)()ZP preferentially to NI, but the ET path was completely switched toward PI in F(-)-coordinated form without a serious drop in the rate, constituting a novel ET-switching molecular system.

Journal Article↗
PubMed2000

Synthesis of 6-acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)- 3-piperidinecarboxylic acids related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.

[reaction: see text] 6-Acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)-3-piperidinecarboxylic acids (8 and 9) have been synthesized starting from natural siastatin B, a bacterial neuraminidase inhibitor isolated from Streptomyces culture in a stereospecific fashion. These compounds are related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.

Acetamides↗
PubMed2000

Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation.

Signals transmitted by class II major histocompatibility complex are important regarding cell function related to antigen presentation. We examined effects of DR-mediated signaling on Ig production from B cells. Cross-linking HLA-DR molecules on B cells by solid-phase anti-HLA-DR monoclonal antibodies, led to an increased production of IgM, without proliferation or apoptosis. This event was accompanied by an enhanced expression of both membrane- and secretory-type IgM heavy chain mRNA. When peptide-pulsed B cells were co-incubated with an HLA-DR-restricted T cell clone treated by the protein synthesis inhibitor emetine, peptide-induced de novo expression of lymphokines and cell-surface molecules on T cells can be neglected. CD40-CD154 interaction was not involved in IgM enhancement, in such a system. The protein-tyrosine kinase inhibitors and the Syk inhibitor piceatannol, but not the Src inhibitor PP2 had a marked inhibitory effect on IgM secretion. Furthermore, ligation of HLA-DR on B cells using the F(ab')2 fragment of anti-DR monoclonal antibody, enhanced Syk activity. Our data suggest that HLA-DR on B cells not only present antigenic peptides to T cells, but also up-regulate IgM production, in association with Syk activation and without the involvement of Src kinases, hence the possible physiological relevance of Src-independent Syk activation.

Animals↗
PubMed2000

Increased phospholipase D2 activity during hypoxia-induced death of PC12 cells: its possible anti-apoptotic role.

During hypoxic incubation (1% O2) of PC12 cells, the PLD activity was transiently increased within 12h, followed by a gradual decrease. In the in vitro assay, the increased PLD activity was independent of GTPgammaS required for PLD1 or of oleic acid for PLD(OA), suggesting the activation of PLD2. The level of PLD2 protein showed no change up to 12h but a gradual decrease after 24 h. Pretreatment of cells with S. chromofuscus PLD resulted in inhibition of hypoxia-induced apoptotic cell death. In contrast, 1-butanol, but not 2-butanol, potentiated cell death. Moreover, the number of apoptotic cells significantly reduced in PC12 cells over-expressing PLD2. These results raise the possibility that PLD2 activation may play an anti-apoptotic role in hypoxia-induced cell death.

1-Butanol↗
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↗