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Biomedical subjects

H Ueno

Publications and source records attributed to H Ueno.

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

Targeted transarterial oily chemoembolization for small foci of hepatocellular carcinoma using a unified helical CT and angiography system: analysis of factors affecting local recurrence and survival rates.

OBJECTIVE: We assessed the local recurrence rate after a single targeted transarterial oily chemoembolization for small hepatocellular carcinoma with the unified helical CT and angiography system and analyzed the factors affecting the local recurrence rate and survival rate with Cox proportional hazards model. MATERIALS AND METHODS: For 54 consecutive patients with 71 small hepatocellular carcinomas (< or = 5 cm) with no more than two associated lesions, targeted oily chemoembolization was performed with an emulsion of doxorubicin hydrochloride mixed with iodized oil or a suspension of zinostatin stimalamer followed by gelatin sponge particles. When local recurrence or a new lesion appeared, follow-up targeted oily chemoembolization was performed. RESULTS: For 52 of 71 lesions, the catheterization to a subsegmental or more distal feeding artery could be performed. Local recurrence was recognized in 33.2% at 1 year and 37.8% at 2 and 3 years. The significant factors that affected local recurrence were tumor size (p = 0.005) and degree of deposition of iodized oil within the lesion (p = 0.049). The survival rates at 1, 2, and 3 years were 93.3%, 77.1%, and 77.1%, respectively. The significant factors affecting survival rate were tumor thrombus in large vessels (p = 0.0001), appearing after the first chemoembolization, and maximum tumor size (p = 0.022). CONCLUSION: Single targeted transarterial oily chemoembolization with the unified helical CT and angiography system had a low local recurrence rate for small hepatocellular carcinoma, and follow-up embolization resulted in a good survival rate. Tumor size along with degree of intratumoral iodized oil deposition and tumor thrombus along with maximum tumor size were significant factors affecting local recurrence and survival rate, respectively.

Aged↗
PubMed2001

[Gene therapy for acute myocardial infarction].

For patients with myocardial infarction, direct angioplasty(PTCA plus stent implantation) has become common practice in Japan. For a better prognosis, inhibition of thrombosis and restenosis in the afflicted coronary artery, salvage of ischemic myocardium, and suppression of myocardial remodeling are all highly desirable. Transfer of genes for molecules appropriate for each of the above pathological conditions is a potential effective therapy. The combined use of a recombinant protein and gene transfer of anti-thrombosis molecule into the injured artery may be an effective and practical local therapy without systemic side-effects. Angiogenesis gene therapy with an aid of endothelial progenitor cells will soon be used in the clinic, while sometime in the future replacement of the myocardial infarct with engineered fresh tissue could be the ultimate therapy.

Angiogenesis Inducing Agents↗
PubMed2001

[Left ventriculoplasty for non-ischemic cardiomyopathy with severe heart failure in 70 patients].

OBJECTIVES: Treatment of cardiac failure due to non-ischemic cardiomyopathy by left ventriculoplasty using partial left ventriculectomy (Batista operation) or septal anterior ventricular exclusion was evaluated. METHODS: Left ventriculoplasty was performed in 70 patients (59 men and 11 women with a mean age of 51 years) from December 1996 to June 2000. Preoperative New York Heart Association (NYHA) functional class was IV in 43 patients including 29 receiving inotropic support, and class III in 27 patients. Nineteen patients required emergency surgery because of on-going shock and 51 patients were operated electively. Combined cardiac procedures were mitral valve reconstruction in 62 patients (45 replacements, 17 repairs), tricuspid annuloplasty in 37, and aortic valve replacement in 4. The initial 24 patients underwent typical Batista operation regardless of myocardial viability. The other 46 patients underwent selective ventriculoplasty to excise or exclude the weakest part according to the findings of the intraoperative echo-guided volume reduction test. RESULTS: The intraaortic balloon pump was used in 12 patients and the left ventricular assist device in 2 patients. Three (5.9%) of the 51 patients who underwent elective operation and 12 (63.2%) of the 19 patients with emergency operation died in the hospital, giving an overall hospital mortality of 21.4% (15/70). Hospital mortality was reduced from 33.3% (8/24) in the initial 24 patients to 15.2% (7/46) in the recent 46 patients with the volume reduction test. Mean ejection fraction increased from 22.2 +/- 6.7% to 29.6 +/- 6.0%. Diastolic dimension decreased from 81.1 +/- 9.5 to 69.8 +/- 19.2 mm. End-diastolic and systolic volume indices decreased from 199.0 +/- 47.9 to 124.1 +/- 34.9 ml/m2 and from 154.0 +/- 41.2 to 89.3 +/- 31.7 ml/m2, respectively, at one postoperative month in the 55 hospital survivors. The mean pulmonary capillary wedge pressure decreased from 25.6 +/- 7.8 to 13.6 +/- 4.5 mmHg. Serum brain natriuretic peptide decreased from 999 +/- 647 preoperatively to 547 +/- 362 pg/ml one month after the operation. Thirteen patients (18.6%) died in the late period mainly due to heart failure. Among the 42 survivors, 37 patients returned to NYHA functional class I-II, and cardiac events were rare after one postoperative year. Actuarial survivals at 3 years in elective and emergency operations were 71.9% and 33.3%, respectively. CONCLUSIONS: Left ventriculoplasty is acceptably safe for elective operation and clinical improvement can be obtained by proper surgical procedures and careful postoperative medical treatment.

Adolescent↗
PubMed2001

Demonstration of genome DNA diversity of strains of urease-positive thermophilic Campylobacter isolated from the natural environment by pulsed-field gel electrophoresis analysis.

Pulsed-field gel electrophoresis (PFGE) analysis was carried out after separate digestion with Apa I, Sal I and Sma I of the genomic DNA from sixteen isolates of urease-positive thermophilic Campylobacter (UPTC) obtained from the natural environment, namely from oysters and mussels, in Northern Ireland. Five NCTC strains previously isolated in England were used for the analysis. Although the eight isolates of UPTC in Northern Ireland and a strain of UPTC in England showed that one or no fragments appeared after digestion with Apa I around 1,900 to 1,640 kb region of the gel, Apa I was shown to cut the genomic DNA from all of the other twelve strains of UPTC and Sal I and Sma I from all of the 21 strains in a distinctly different and distinguishable manner. Consequently, the present study clearly demonstrated that the sixteen isolates of UPTC in Northern Ireland and the five strains in England gave the diversity of the genomic DNA by using PFGE. Some strains of UPTC examined were shown to carry genomes from 1.6 to 1.9 Mb in length, thus the heterogeneous profiles of PFGE and the length of the genomes are thought to occur among the isolates of UPTC in Northern Ireland, as well as among the five representative strains of UPTC from NCTC.

Animals↗
PubMed2000

Transfection of the plasma-type platelet-activating factor acetylhydrolase gene attenuates glutamate-induced apoptosis in cultured rat cortical neurons.

Using an adenoviral vector, we induced overexpression of the plasma type of platelet-activating factor acetylhydrolase in cultured rat neurons. Neurons overexpressing this enzyme showed a decrease in glutamate-induced injury, mainly, apparent as decreased apoptosis. Reduction of lipid peroxidation by this enzyme and protection of mitochondrial function were demonstrated, and these may be the basis of the resistance to glutamate-induced neuronal injury that we observed.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Second stalk of ATP synthase. Cross-linking of gamma subunit in F1 to truncated Fob subunit prevents ATP hydrolysis.

ATP synthase consists of two portions, F(1) and F(o), connected by two stalks: a central rotor stalk containing gamma and epsilon subunits and a peripheral, second stalk formed by delta and two copies of F(o)b subunits. The second stalk is expected to keep the stator subunits from spinning along with the rotor. We isolated a TF(1)-b'(2) complex (alpha(3)beta(3)gammadeltaepsilonb'(2)) of a thermophilic Bacillus PS3, in which b' was a truncated cytoplasmic fragment of F(o)b subunit, and introduced a cysteine at its N terminus (bc'). Association of b'(2) or bc'(2) with TF(1) did not have significant effect on ATPase activity. A disulfide bond between the introduced cysteine of bc' and cysteine 109 of gamma subunit was readily formed, and this cross-link caused inactivation of ATPase. This implies that F(o)b subunit bound to stator subunits of F(1) with enough strength to resist rotation of gamma subunit and to prevent catalysis. Contrary to this apparent tight binding, some detergents such as lauryldodecylamine oxide tend to cause release of b'(2) from TF(1).

Adenosine Triphosphate↗
PubMed2000

Total synthesis of the antitumor antibiotic (+/-)-fredericamycin A by a linear approach.

A linear approach to the total synthesis of racemic fredericamycin A (1) through the oxidative intramolecular [4 + 2] cycloaddition of a (phenylthio)acetylene-cobalt complex is described, which is applicable for the asymmetric total synthesis of naturally occuring 1. The highlight of this work is the aromatic Pummerer-type reaction with 1-ethoxyvinyl chloroacetate, which effects the introduction of the oxygen functional group to the internal B-ring of the highly functionalized, congested polyaromatic ABC-ring moiety.

Antibiotics, Antineoplastic↗
PubMed2000

A possible role for centrosome overduplication in radiation-induced cell death.

Radiotherapy plays a key role in the treatment of many tumors; however, the precise mechanisms responsible for radiation-induced cell death remain uncertain. We have reported previously that ionizing radiation induces centrosome overduplication in human tumor cells. The present study was designed to elucidate a possible link between centrosome dysregulation and radiation-induced cell death. Exposure to 10 Gy gamma-radiation resulted in a substantial increase in cells containing an abnormally high number of centrosomes in a variety of cell lines derived from different types of human solid tumors. These aberrant centrosomes contribute to the assembly of multipolar spindles, thereby causing an unbalanced division of chromosomes and mitotic cell death characterized by the appearance of multi- or micronucleated cells. An extensive analysis of a panel of 10 tumor cell lines revealed a positive correlation between the fraction of cells with multiple centrosomes and the fraction with these nuclear abnormalities after irradiation. When the centrosome overduplication was blocked by enforced expression of p21Waf1/Cip1, the radiation-induced lethality was drastically rescued. Taken together, these results indicate that centrosome overduplication may be a critical event leading to mitotic failure and subsequent cell death following exposure to ionizing radiation.

Adenoviridae↗
PubMed2000

Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ.

Antiangiogenic therapy shows promise as a strategy for cancer treatment. We constructed an adenovirus (AdVEGF-ExR) expressing the entire extracellular domain of the human vascular endothelial growth factor (VEGF) receptor (flt-1) fused to the Fc portion of human IgG. The soluble receptor secreted from AdVEGF-ExR-infected cells bound to VEGF and inhibited VEGF-induced DNA synthesis in endothelial cells. When human lung cancer cell line H157, which produces not only VEGF but also fibroblast growth factor 2 and interleukin 8 at substantial levels, was infected with AdVEGF-ExR, cell growth in vitro was not affected. However, when H157 cells infected with AdVEGF-ExR were injected s.c. into nude mice, tumor formation stopped on the 10th day after reaching a certain size (about 100 mm3), and tumor size declined gradually thereafter. When AdVEGF-ExR was injected into skeletal muscle and uninfected H157 cells were injected s.c., the soluble receptor was detectable in the circulating blood for 3 weeks, tumor growth ceased after 10 days, and tumor size declined thereafter. Histological examination revealed that intratumor angiogenesis was markedly suppressed, and apoptosis was enhanced. Using the same experimental protocol, a significant suppression of tumor growth was also seen in four of five other lung cancer cell lines, some of which secreted VEGF at nominal levels, at least under normoxic conditions in vitro. Our results demonstrate that adenovirus-mediated expression of a soluble VEGF receptor in a remote organ could inhibit tumor angiogenesis and enhance apoptosis and thereby suppress tumor growth in vivo. Adenovirus-mediated overexpression of a soluble VEGF receptor in a remote organ may have the potential to be a feasible and effective strategy for cancer treatment.

Adenoviruses, Human↗
PubMed2000

Defects in TGF-beta signaling overcome senescence of mouse keratinocytes expressing v-Ha-ras.

Previous studies have shown that TGFbeta1 expression is upregulated in mouse keratinocytes infected with a v-rasHa retrovirus, although the functional significance of this has not been clear. Here we show that v-rasHa retrovirus transduced primary mouse keratinocytes undergo hyperproliferation followed by a TGFbeta1 dependent G1 growth arrest and senescence. The growth arrest is accompanied by a 15-fold increase in total TGFbeta1 secreted and a fourfold increase in secreted active TGFbeta1. When cultured in the presence of a neutralizing antibody to TGFbeta1, the senescence response is suppressed. Levels of the TGFbeta1 target p15ink4b increase during senescence as does association of this kinase inhibitor with cyclinD/cdk4 complexes. However, p16ink4a, p53 and p19ARF expression also increase during senescence. Genetic analysis shows that TGFbeta1 null and dominant negative TbetaBRII expressing v-rasHa keratinocytes resist the G1 growth arrest and do not senescence. This resistance is associated with low expression of p15ink4b and p16ink4a, constitutive Rb phosphorylation and high levels of cdk4 and cdk2 kinase activity. In contrast, inactivation of TGFbetabeta1 secretion or response does not block the induction of p53 and p19ARF, but the level of p21waf1, a p53 target gene, is reduced in cyclin D/cdk4 and cyclin E/cdk2 complexes. Thus, although multiple senescence pathways are activated in response to a ras oncogene, inactivation of TGFbeta1 secretion or response is sufficient to block the senescence program. Since v-rasHa transduced TGFbeta1-/- keratinocytes form squamous cell carcinomas following skin grafting, these results suggest that in mouse keratinocytes, defects in TGFbeta1 signaling accelerate malignant progression by overcoming oncogene induced replicative senescence.

Animals↗
PubMed2000

Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo.

OBJECTIVE: This study was designed to examine whether or not adenovirus-mediated gene transfer of C-type natriuretic peptide (CNP) can prevent coronary restenotic changes after balloon injury in pigs in vivo. BACKGROUND: Gene therapy to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) might be useful but requires a method applicable for in vivo gene delivery into the coronary artery as well as the efficient vector encoding a potent antiproliferative substance. We tested whether the adenovirus-mediated gene transfer of CNP by use of an infiltrator angioplasty balloon catheter (IABC) might prevent the coronary restenotic changes after balloon injury. METHODS: Balloon angioplasty was performed in the left anterior descending and the left circumflex coronary artery in pigs. Immediately after the balloon injury, adenovirus solution encoding either CNP (AdCACNP) or beta-galactosidase (AdCALacZ) gene was injected with IABC into the balloon-injured coronary segments. Expression of CNP was assessed by immunohistochemical staining and cyclic guanosine 3',5'-monophosphate (cGMP) measurement. Coronary restenotic changes were evaluated by both angiographic and histological examinations. RESULTS: CNP was highly expressed in the media and the adventitia of the coronary artery at the AdCACNP-transfected but not at the AdCALacZ-transfected segment. In the AdCALacZ-transfected segment, vascular cGMP levels tended to be reduced as compared with the untreated segment, whereas in the AdCACNP-transfected segment, vascular cGMP levels were restored. Angiographic coronary stenosis was significantly less at the AdCACNP-transfected than at the AdCALacZ-transfected segment. Histological examination revealed that this was achieved primarily by the marked inhibition of the geometric remodeling of the coronary artery by the CNP gene transfer. CONCLUSIONS: Adenovirus-mediated CNP gene transfer with the IABC system may be a useful gene therapy to prevent restenosis after PTCA in vivo.

Adenoviridae↗
PubMed2000

Out of plane measurements of the decay neutron from the giant resonance in the 12C(e,e(')n)11C reaction

Out of plane measurements of the angular correlations for the 12C(e, e(')n) reaction have been performed for the first time in the giant resonance region. The cross sections were directly separated into the longitudinal and transverse, longitudinal-transverse, and transverse-transverse components. The cross section at the peak of the giant resonance ( omega = 22.5 MeV) has been found to be almost all longitudinal. It was reproduced by the multipole expansion with E0 and E2 components besides E1. The longitudinal-transverse component might have a maximum around 24 MeV. The transverse-transverse component is very small over the giant resonance.

Journal Article↗
PubMed2000

A soluble transforming growth factor beta receptor expressed in muscle prevents liver fibrogenesis and dysfunction in rats.

We demonstrated that local expression of a dominant-negative type II TGF-beta receptor prevents live fibrogenesis and dysfunction in dimethylnitrosamine-treated rats. Using the same model, we have now tested whether a soluble TGF-beta receptor expressed in skeletal muscle can effectively suppress TGF-beta signaling in a remote organ (the liver). We constructed an adenovirus expressing an entire ectodomain of human TGF-beta type II receptor fused to the Fc portion of human IgG (AdTbeta-ExR). This soluble receptor secreted from AdTbeta-ExR-infected cells bound TGF-beta and blocked TGF-beta-signaling in vitro. After intramuscular injection of AdTbeta-ExR in rats, the soluble receptor protein was detectable in the blood for at least 3 weeks. When such rats were treated with dimethylnitrosamine, liver fibrosis was markedly attenuated without apparent systemic or local side effects. The hepatic hydroxyproline content was reduced to a level indistinguishable from that achieved by local expression of the dominant-negative TGF-beta receptor. Since a qualitatively and quantitatively similar suppression was achieved by the two methods, it may be concluded that the new strategy can achieve a complete inhibition of TGF-beta signaling under pathophysiological conditions in vivo. This strategy should facilitate clarification of the role of TGF-beta in vivo in various organs where direct gene transfer seems to be difficult.

Animals↗
PubMed2000

Suppression of malignant growth potentials of v-Src-transformed human gallbladder epithelial cells by adenovirus-mediated dominant negative H-Ras.

Although Src transformation of NIH3T3 mouse fibroblasts has been shown to be dependent on Ras function, the signaling mechanism whereby Src induces malignant transformation of human epithelial cells still remains unclear. In the present study, we analyzed the functional role of Ras, which acts downstream of Src in intracellular signaling, in the acquisition of fully neoplastic potentials by v-Src-transformed human gallbladder epithelial cells (HAG/src3-1) by infecting these cells with replication-defective adenovirus vector expressing dominant negative H-Ras (AdCARasY57). High efficiency of gene transduction was demonstrated with the adenovirus vector containing beta-gal gene insert (AdCALacZ). On infection with AdCARasY57, the activity of mitogen-activated protein (MAP) kinase, a major downstream event triggered by Ras, was markedly inhibited over 7 days, indicating that the inhibition of Ras function by AdCARasY57 remains active during this period. AdCARasY57 did not inhibit the monolayer growth of HAG-1 cells transfected with activated H-ras, but inhibited the HAG/src3-1 cells by 30%, as compared with cells infected with AdCALacZ as a control. This growth inhibition by AdCARasY57 was strengthened nearly twofold on surfaces coated with an antiadhesive polymer (poly 2-hydroxyethylmethacrylate) that can quantitate anchorage-independent growth, and was much more pronounced up to 95% when assayed in soft agar. The HAG/src3-1 cells transfected with beta-gal gene produced tumors in nude mice within 4 weeks after implantation, whereas cells infected with AdCARasY57 failed to form tumors during this period. These findings show that Ras function is essential for v-Src-induced anchorage-independent growth in vitro as well as tumorigenesis in vivo, and that mitogenic activity driven by v-Src is not solely dependent on MAP kinase pathway. Because anchorage-independent growth correlates with tumor growth in vivo as well as metastatic potential, targeting Ras would be potentially useful for the treatment of human tumors with elevated Src tyrosine kinase activity.

Adenoviridae↗
PubMed2000

ZAP-70 is required for calcium mobilization but is dispensable for mitogen-activated protein kinase (MAPK) superfamily activation induced via CD2 in human T cells.

Stimulation with specific pairs of anti-CD2 antibodies can induce T cell activation and proliferation. In this study, we investigate the significance of ZAP-70 in CD2 signaling using ZAP-70-deficient T cells derived from a CD8-deficient patient and show that ZAP-70 is necessary for cellular proliferation and cytokine production in T cells stimulated via CD2. Biochemical analyses show that CD2 stimulation induces activation of mitogen-activated protein kinase (MAPK) superfamily in ZAP-70-deficient T cells, indicating that a ZAP-70-independent pathway(s) exists for MAPK superfamily activation via CD2. In contrast, intracellular Ca(2+) mobilization and activation of nuclear factor of activated T cells (NFAT) upon CD2 triggering were impaired in T cells lacking ZAP-70. Furthermore, we found that pharmacological Ca(2+) elevation combined with CD2 stimulation restored NFAT activation and subsequent cytokine production in ZAP-70-deficient T cells. These results indicate that in CD2 signaling, ZAP-70 plays an essential role in Ca(2+) mobilization and NFAT activation.

Animals↗
PubMed2000

Radiotherapy for hepatocellular carcinoma.

PURPOSE: To retrospectively evaluate the effectiveness of radiotherapy with or without transarterial embolization (TAE) and/or percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma who were ineligible for surgery. PATIENTS AND METHODS: From October 1984 to November 1997, 62 patients underwent radiotherapy receiving 50 to 70 Gy in 25 to 35 treatments with or without transarterial embolization and/or percutaneous ethanol injection and were followed for a median period of 8.6 months (1.5 to 92 months). RESULTS: Overall median survival rates were 9.5 months. Significant prognostic factors were the extent of pretreatment liver function impairment, radiation field size and the existence of tumor thrombosis. Six-month and 1-year local control rates were 67 and 54%, respectively. Seven of the 8 patients who suffered from hepatic failure had poor pretreatment liver functions. CONCLUSION: Radiotherapy with or without transarterial embolization and/or percutaneous ethanol injection appears effective in controlling hepatocellular carcinoma and prolonged survival. Individualized treatment strategies are presented depending on the tumor presentation and the degree of liver function impairment.

Aged↗