Inhibition of human pancreatic cancer growth by the adenovirus-mediated introduction of a novel growth suppressing gene, tob, in vitro.
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Adenoviridae↗
Biomedical subjects
S Asano
Publications and source records attributed to S Asano.
[Successful surgical correction for an incomplete endocardial cushion defect in an elderly patient].
A 72-year-old female who presented with symptoms of severe congestive heart failure, was subsequently diagnosed as having an incomplete endocardial cushion defect. A severe left-to-right shunt and mitral and tricuspid valve regurgitation were noted. Closure of the ostium primum defect, mitral valve replacement, and tricuspid valve annuloplasty were performed simultaneously. The postoperative course was uneventful. A review of literature revealed that this is the oldest such surgical patient described in Japan to date. We believe that surgical correction can be effective even in elderly patients.
Aged↗
[One-stage surgery for Stanford type-A aortic dissection, annulo-aortic ectasia, and chronic constrictive pericarditis--a case report].
A case is reported of a rare combination of chronic constrictive pericarditis and aortic dissection. A 23-year-old male was diagnosed with constrictive pericarditis and annulo-aortic ectasia concomitant with type-A dissection. A pericardiectomy was performed under cardiopulmonary bypass, and an aortic segment, from the root to the arch, was totally replaced by a composite graft using selective cerebral perfusion. Both procedures were performed in one stage. An aged clot was found in the pericardial cavity. Sustained rupture of the aortic dissection into the pericardial cavity is considered to be a possible explanation for the development of constrictive pericarditis. The postoperative course was uneventful and the patient was discharged 34 days after the operation.
Adult↗
The effect of Y-25510 injection on the serum levels of some cytokines in healthy adult volunteers.
OBJECTIVE: Y-25510 was administered by means of an intravenous drip infusion to healthy adult male volunteers at a dose of 40, 80 or 160 mg in a single-dose study, and at a dose of 160 mg once a day for 7 days in a multiple-dose study. RESULTS: Serum levels of interleukin (IL)-1beta, IL-6 and IL-10 were significantly increased, but there was no change in leukocyte and platelet counts. The peak serum concentration of IL-1beta was nearly maximum at the single doses of 40 and 80 mg, and at the multiple dose of 160 mg per day. The peak serum concentration of IL-6 increased in a dose-dependent manner at a dose of 40 mg or more. For the multiple-dose study, the serum level of IL-10, which remained unchanged in the placebo group, began to increase in the Y-25510 group following the maximum serum level of IL-1beta and IL-6. There were no clinically relevant differences in body temperature and blood pressure after the administration of Y-25510. CONCLUSION: These findings that leukocyte and platelet counts never increased, despite the increment of the IL-1beta and IL-6 production after the administration of Y-25510, may be explained in part by the negative feedback mechanism induced by IL-10.
Adjuvants, Immunologic↗
Expression of manganese superoxide dismutase in esophageal and gastric cancers.
The tumor-killing activity of radiotherapy and chemotherapy for cancer is closely associated with the production of active oxygen, and the relation between therapeutic resistance and active oxygen scavengers produced by the tumor itself is gaining more attention. It is considered that manganese superoxide dismutase (MnSOD) protects host cells from oxidative stress, in synergy with other antioxidant enzymes. In this study, we used a quantitative polymerase chain reaction assay to measure MnSOD mRNA in resected specimens from patients with esophageal and gastric cancers. In both esophageal and gastric cancers, the level of MnSOD mRNA was significantly elevated in cancer tissue compared to non-cancer tissue (P < 0.01). In gastric cancer tissue, the MnSOD mRNA level was significantly higher than in esophageal cancer tissue (P < 0.01). The significance of MnSOD in cancer tissue was investigated further by measuring MnSOD content in resected specimens using an enzyme-linked immunosorbent assay, and by examining its location by an immunohistochemical method. Upregulation of MnSOD in cancer tissue most likely serves as a protective mechanism against anti-cancer therapies known to produce superoxide radicals as a key component of their tumor-killing activity.
Adenocarcinoma↗
Analysis of genetic information of an insect picorna-like virus, infectious flacherie virus of silkworm: evidence for evolutionary relationships among insect, mammalian and plant picorna(-like) viruses.
We synthesized the cDNAs of an insect picornavirus, infectious flacherie virus of silkworm (IFV), genomic RNA and inserted it into a bacterial plasmid (pUC119). The 9,650 nucleotides (nts) sequence except for the poly(A) tail was obtained from the cloned cDNAs, and the sequence integrity was confirmed by primer extension and direct RNA sequencing. The sequence has a large open reading frame (ORF) of 9,255 nts (3,085 codons) flanked by the short 5' non-coding region (156 nts) and by the rather long 3' non-coding (239 nts). The structural proteins VP3, 4, 1 and 2 were located at the N-terminus of the polyprotein in this order and were preceded by a tentative small peptide. Computer analysis identified the sequences similar to the consensus sequences of 2C (helicase?), 3C (protease), and 3D (RNA polymerase) conserved among mammalian and plant picorna(-like) viruses. In addition, the predicted genome organization of IFV was quite similar to those of picornaviruses. Further analyses of the characteristics of the genome structure and a tentative phylogenetic tree constructed on the basis of the amino acid sequence similarity emphasized the evolutionary relationships among the insect and plant viruses.
Adenoviridae↗
Gene transfer of alpha interferon into hematopoietic stem cells.
Gene transfer or gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. IFN-alpha has been used in the management of leukemia, and gene transfer of the IFN-alpha gene into hematopoietic progenitor cells may have great potential for the treatment of chronic myelogenous leukemia (CML). Therefore, we examined the ability of adenovirus (Ad)-IFN-alpha gene construct to transfect normal bone marrow hematopoietic CD34+ stem cells and the production of IFN-alpha protein by these cells. Ad-cytomegalovirus (CMV) promoter-driven IFN-alpha at multiple doses was assessed to transfect highly purified CD34+ cells in liquid culture. Optimal transduction of CD34+ cells with the AdCMV-IFN-alpha construct was achieved using 120 plaque forming units (pfu). Flow cytometric determinations revealed that there was no significant difference in CD34+ cell viability for the 8 or 12-h transfection periods. Immunoassay of IFN-alpha produced by CD34+ cells shows that IFN-alpha levels increased several fold in transfected cells and this was not seen in CD34+ cells transfected with the heme oxygenase gene (HO-1). These in vitro data suggest that adenovirus-mediated gene transfer of IFN-alpha into hematopoietic stem cells can be achieved and that the IFN-alpha protein is produced by viable CD34 progenitor cells.
Adenoviridae↗
Establishment of novel cell lines derived from two patients with chronic myelogenous leukemia in blast crisis; IMS-BC1 and IMS-BC2 which exhibit markedly different sensitivity to apoptosis.
We established two novel cell lines, designated as IMS-BC1 and IMS-BC2, from two patients with chronic myelogenous leukemia in blast crisis. The two cell lines were positive for CD13 and CD33 and negative for CD34 and HLA-DR by surface marker analysis. IMS-BC1 had four Philadelphia (Ph1) chromosomes and a breakpoint within the 3'-portion of M-bcr, and IMS-BC2 had five Ph1 chromosomes and two breakpoints within the 3'- and 5'-portions of M-bcr. Both cell lines' growth activities were moderately suppressed by IFN-alpha. The proliferation of IMS-BC2 was inhibited by IFN-gamma and apoptosis was induced within 72 h, while IMS-BC1 was resistant to IFN-gamma. Fibronectin inhibited the proliferation of the two cell lines at higher than 10 micrograms/ml, but only IMS-BC2 showed apoptosis. Transforming growth factor-beta inhibited the proliferation of IMS-BC2 resulting in apoptosis, while it inhibited that of IMS-BC1 moderately but failed to induce apoptosis. All-trans retinoic acid (ATRA) inhibited the proliferation of IMS-BC2 at very low concentration (10(-17) mol/l) and induced apoptosis at doses higher than 10(-9) mol/l within 72 h without terminal differentiation, while IMS-BC1 was completely resistant to ATRA. The two cell lines showed different responses to growth inhibitory cytokines and factors. These cell lines should prove useful in the analysis of mechanisms of apoptosis induced by growth inhibitory cytokines and factors.
Adolescent↗
A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo.
We have constructed an allosterically controllable novel enzyme (designated maxizyme) that can be transcribed in vivo under the control of a human tRNA(Val) promoter. The maxizyme has sensor arms that can recognize target sequences, and in the presence of such a target sequence only, it can form a cavity that can capture catalytically indispensable Mg2+ ions. As a target for a demonstration of the potential utility of the maxizyme, we chose BCR-ABL mRNA, the translated products of which cause chronic myelogenous leukemia. Only the maxizyme (but not conventional ribozymes) had extremely high specificity and high-level activity, not only in vitro but also in cultured cells including BV173 cells derived from a patient with a Philadelphia chromosome. The maxizyme induced apoptosis only in leukemic cells with this chromosome.
Allosteric Regulation↗
Vaccine effect of granulocyte-macrophage colony-stimulating factor or CD80 gene-transduced murine hematopoietic tumor cells and their cooperative enhancement of antitumor immunity.
To develop immunogene therapy targeting minimal residual hematopoietic tumor cells in patients, we transduced murine GM-CSF or CD80 gene into murine WEHI 3B myelomonocytic leukemia and EL-4 thymic lymphoma cells using retroviral vectors and evaluated their effects on inducing antitumor responses in syngeneic host mice. Subcutaneously injected GM-CSF- and CD80 gene-transduced WEHI 3B (GMCSF/WEHI/3.2 or CD80/WEHI/1.8, respectively) cells lost their original tumorigenicity in immunocompetent syngeneic mice. Results from tumor inoculation experiments using athymic nude mice suggested that the rejection of GMCSF/WEHI/3.2 in immunocompetent mice depended fully on T cells and that of CD80/WEHI 1.8 depended partly on T cells and partly on NK cells. In both WEHI 3B and EL-4 models, irradiated GM-CSF gene-transduced cells provided strong immuno-protection against wild-type cells, but irradiated CD80 gene-transduced cells did not. A remarkably high cooperative effect was obtained when irradiated GMCSF/EL-4 and CD80/EL-4 were inoculated together. These results suggested that the tumor vaccine effect is efficiently enhanced by GM-CSF gene transduction and CD80 gene transduction induces some protective antitumor immunity in co-operation with GM-CSF gene transduction.
Animals↗
IL-6 and SCF exert different effects on megakaryocyte maturation.
Megakaryocytic maturation has two aspects, nuclear maturation and cytoplasmic maturation, both of which are affected by several thrombopoietic cytokines. We cultured murine bone marrow cells separated by BSA velocity sedimentation which contained more immature megakaryocytes with lower ploidy in order to study the effects of rhIL-6 and rmSCF on the two aspects of megakaryocyte maturation. During culture with rhIL-6 or rmSCF for 4 d, the megakaryocytes underwent endomitosis, resulting in DNA polyploidization. These two cytokines had different effects on cytoplasmic maturation. Flow cytometry showed that the megakaryocytes cultured with rhIL-6 became larger and had a more complex intracellular structure than those cultured with rmSCF. Morphological studies showed that the megakaryocytes cultured with rhIL-6 were larger and more granular, whereas those cultured with rmSCF were smaller and more basophilic. rhIL-6 promoted cytoplasmic process formation by the megakaryocytes, but rmSCF did not. Analysis of transcripts of PF-4 and GPIIb by RT-PCR suggested that rmSCF kept more megakaryocytes at the protein synthesis stage than did rhIL-6. Based on our findings, these cytokines exert different effects on megakaryocytic cytoplasmic maturational events.
Animals↗
Involvement of calcineurin in Ca2+ paradox-like injury of cultured rat astrocytes.
The Ca2+/calmodulin-dependent phosphatase calcineurin may have physiological and pathological roles in neurons, but little is known about the roles of the enzyme in glial cells. We have previously reported that reperfusion of cultured astrocytes in Ca2+-containing medium after exposure to Ca2+-free medium caused Ca2+ influx followed by delayed cell death. In this study, we examined if calcineurin is involved in this Ca2+-mediated astrocytic injury. FK506, an inhibitor of calcineurin, protected cultured rat astrocytes against paradoxical Ca2+ challenge-induced injury in a dose-dependent manner (10(-10)-10(-8) M). Cyclosporin A at 1 microM mimicked the effect of FK506. Rapamycin (1 microM) did not affect astrocyte injury, but it blocked the protective effect of FK506. Deltamethrin (20 nM), another calcineurin inhibitor, had a similar protective effect, whereas okadaic acid did not. FK506 affected neither paradoxical Ca2+ challenge-induced increase in cytosolic Ca2+ level nor Na+-Ca2+ exchange activity in the cells, suggesting that the calcineurin is involved in processes downstream of increased cytosolic Ca2+ level. Immunochemical studies showed that both calcineurin A (probably the A beta2 isoform) and B subunits were expressed in the cells. It is concluded that calcineurin is present in cultured astrocytes and it has a pathological role in the cells.
Animals↗
Cyclin D1 overexpression detected by a simple competitive reverse transcription-polymerase chain reaction assay for lymphoid malignancies.
t(11;14)(q13;q32) observed in B-cell malignancies is associated with cyclin D1 (bcl-1, PRAD1, CCND1) overexpression. We devised a simple competitive reverse transcription-polymerase chain reaction (RT-PCR) assay for rapid detection of cyclin D1 overexpression. Sharing a single upstream primer derived from a homologous sequence in cyclins D1, D2 and D3, each PCR product serves as a competitor and cyclin D1 overexpression is determined by comparing the intensities of the three amplified products. We analyzed cyclin D1 in clinical specimens from 104 patients with lymphoid malignancies. Cyclin D1 overexpression was evident in 13 of 104 (7/72 non-Hodgkin's lymphomas, 0/6 adult T-cell lymphoma/leukemias, 0/4 Hodgkin's diseases, 0/11 acute lymphoblastic leukemias, 3/4 multiple myelomas, 1/2 Waldenström's macroglobulinemias, 1/2 prolymphocytic leukemias and 1/3 chronic lymphocytic leukemias). Among 72 patients for whom cytogenetic studies had been done, all 7 patients with t(11;14) were positive. The relative expression levels of D-type cyclins altered dramatically in the presence of t(11;14). Thus, this RT-PCR assay can identify tumors with cyclin D1 overexpression. Cyclin D1 overexpression was frequent in extranodal specimens (11 out of 32 vs. 2 of 72 lymph nodes) and was restricted to specific types of lymphoid malignancies, as observed using other methods. This reliable assay should be suitable to provide clinical guidance for the diagnosis and management of lymphoid malignancies, especially in the case of extranodal involvement.
Adolescent↗
Functional expression of putative H+-K+-ATPase from guinea pig distal colon.
A guinea pig cDNA encoding the putative colonic H+-K+-ATPase alpha-subunit (T. Watanabe, M. Sato, K. Kaneko, T. Suzuki, T. Yoshida, and Y. Suzuki; GenBank accession no. D21854) was functionally expressed in HEK-293, a human kidney cell line. The cDNA for the putative colonic H+-K+-ATPase was cotransfected with cDNA for either rabbit gastric H+-K+-ATPase or Torpedo Na+-K+-ATPase beta-subunit. In both expressions, Na+-independent, K+-dependent ATPase (K+-ATPase) activity was detected in the membrane fraction of the cells, with a Michaelis-Menten constant for K+ of 0.68 mM. The expressed K+-ATPase activity was inhibited by ouabain, with its IC50 value being 52 microM. However, the activity was resistant to Sch-28080, an inhibitor specific for gastric H+-K+-ATPase. The ATPase was not functionally expressed in the absence of the beta-subunits. Therefore, it is concluded that the cDNA encodes the catalytic subunit (alpha-subunit) of the colonic H+-K+-ATPase. Although the beta-subunit of the colonic H+-K+-ATPase has not been identified yet, both gastric H+-K+-ATPase and Na+-K+-ATPase beta-subunits were found to act as a surrogate for the colonic beta-subunit for the functional expression of the ATPase. The present colonic H+-K+-ATPase first expressed in mammalian cells showed the highest ouabain sensitivity in expressed colonic H+-K+-ATPases so far reported (rat colonic in Xenopus oocytes had an IC50 = 0.4-1 mM; rat colonic in Sf9 cells had no ouabain sensitivity).
Animals↗
[New strategies and future direction in hematopoietic stem cell transplantation from unrelated volunteer donor].
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Graft vs Host Disease↗
Intermittent obstruction of the inferior vena cava by congenital anteromedial diaphragmatic hernia: an extremely rare case of Budd-Chiari syndrome in an infant.
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Budd-Chiari Syndrome↗
[Necrotizing lymphadenitis].
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Histiocytic Necrotizing Lymphadenitis↗