Biomedical subjects
Publications and source records attributed to H Doi.
A recently identified subtype of hepatitis C virus, subtype 1d, was found to be common in Indonesia, being isolated from 4 (20%) of 20 and 11 (34%) of 32 patients with chronic hepatitis and liver cirrhosis, respectively. A new group of sequence variants was also identified, although its prevalence ratio was not as high in the area surveyed.
Secondary myelodysplastic syndrome (MDS) with t(9;11)(p22;q23) developed in a child after intensive treatment for B-cell acute lymphoblastic leukemia diagnosed 12 months earlier. His chemotherapy had consisted mainly of cyclophosphamide and methotrexate, but no epipodophyllotoxins. The combination of MDS, the cytogenetic anomaly involving bands at 11q23 and no previous exposure to epipodophyllotoxins represents a unique case of therapy-related leukemia.
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Transglutaminase1 (TGase1) gene is expressed at the late stage of terminal differentiation of epidermal keratinocytes. 12-O-tetradecanoylphorbol-13-acetate (TPA) markedly induced the luciferase activity in cultured rat keratinocytes. FRSK cells, transfected with a luciferase reporter plasmid containing the 0.82-kb 5'-flanking region of the human TGase1 gene, but hardly in non-keratinocytic cells. The TPA-induced luciferase activity was suppressed by retinoic acid, 9-cis retinoic acid, and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Co-transfection with expression plasmids for c-jun and/or c-fos showed that Jun itself induced the luciferase activity, whereas Fos inhibited both the basal and TPA-induced luciferase activity. These results suggested that the signaling systems including protein kinase C, retinoic acid/retinoid-X receptors, and Jun/Fos regulate the transcription of the TGase1 gene.
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A 34-year-old woman was admitted because of pancytopenia with DIC in the 28th week of pregnancy. Bone marrow aspirate demonstrated 81.2% abnormal cells which showed Auer bodies and faggot formation. Chromosomal analysis demonstrated an abnormality, t (15; 17). The patient was diagnosed as having acute promyelocytic leukemia (APL) and started to receive treatment with all-trans retinoic acid (ATRA) 70 mg/body/day per os. She had a cesarean section and gave birth to a female infant in the 29th week of pregnancy. An increase of WBC counts was observed on the 9th hospital day, then chemotherapy with anti-cancer agents was performed additionally. Complete remission was achieved on the 27th hospital day. Management of pregnant patients with APL could be improved by using ATRA instead of conventional combinations of cytotoxic agents.
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Seroepidemiological and laboratory virological evidences strongly suggested that endemicity of HTLV-1 in Nagasaki Japan depends on maternal infant infections via breast milk. The most obvious way to prove this concept was an intervention study with refraining from breast-feeding by carrier mothers. Most infected babies seroconverted by the age of 12 months, which made it possible to diagnose the infection at the age of 12 months for the statistical purpose. Serology and PCR on both adults and children were consistent each other, suggesting the absence of seronegative carriers. The intervention study revealed that approximately 80% of maternal infection was prevented by refraining from breast feeding by carrier mothers. The remaining fraction of infections in formula-fed babies suggested an alternative infection pathway. Although intrauterine infections has been suggested by others to explain the PCR-positive cord blood samples. However, groups of cord blood-positive children and seroconverted children were distinct each other. Therefore, the presence of HTLV-1 provirus in the cord blood can not be a marker of intrauterine infection. Mothers who infected a child has approximately 10 times higher risk of another infection for the next baby than those who did not.
Evolution is, in a sense, to resolve optimization problems. Our neo-Darwinian algorithm based on the mechanics of inheritance and natural selection uses double-stranded DNA-type genetic information to resolve the "knap-sack problem." The algorithm with asymmetrical mutations due to semiconservative DNA-type replication most effectively resolved the problem. Our results strongly suggest that disparity in mutations caused by the asymmetric machinery of DNA replication promotes evolution, in particular of diploid organisms with a high mutation rate, in a small population, and under strong selection pressure.
A case of hilar lung adenocarcinoma was treated by superselective bronchial arterial infusion therapy with cisplatin and epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) using Tracker -18 infusion catheter. The tumor size was reduced on follow-up CT scans. However, EMILE was also distributed to nontumorous lung tissues around the tumor, and a shrinkage of the right upper lobe and elevations of the right hilus and diaphragm followed. No major complaints and clinical complications during and after the treatment occurred. This therapy was safe and effective for local tumor reduction in a case of hilar lung adenocarcinoma.
The effect of heat treatment temperature on bending properties and transformation temperatures of a Ni-Ti alloy wire, 1.0 mm in diameter, was investigated so that superelasticity could be used in orthodontic appliances needing shape memory processes. The heat treatment process was at 713 K for 1.8 ks and between 673 K and 813 K for 1.8 ks. A three-point bending test and differential scanning calorimetry were performed. The transformation temperatures of the wires were lowered with increasing heat treatment temperature. The reverse transformation finishing temperature was below the body temperature with the treatment above 753 K. Residual deflection of the Ni-Ti wire after bending was small with the secondary heat treatment above 733 K. The load in the unloading process was less changeable and increased with the treatment temperature between 733-813 K. Secondary heat treatment in this range was suitable for using superelasticity in expansion arch appliances.
Although the fetal liver has been thought to be the main hemopoietic organ in the embryonal period, whether or not hepatocytes play a major role in hemopoiesis remains obscure. We have established an epithelial cell line from the murine fetal liver, which can support hemopoiesis in vitro. The proliferation of the epithelial cells was promoted synergistically by both epidermal growth factor (EGF) and insulin. The cells were identified as epithelial cells by the presence of desmosomes and tight junctions. Cytoplasmic organelles including small mitochondria and dilated Golgi apparati as well as intercellular canalicular structures similar to bile canaliculus also helped in confirming the hepatic origin of the cell line (designated as FHC). The cells in the primary culture were positive for both alpha-fetoprotein and albumin, indicating the hepatocytic nature of the cell line. Cloned FHC cells were demonstrated to have the ability to maintain hemopoietic progenitors in fetal liver and adult bone marrow in the coculture, and among them, FHC-4D2 clone displayed the greatest activity. Hemopoiesis-supporting function could also be seen even when bone marrow cells were separated from FHC-4D2 cells by nitrocellulose membrane. Column chromatography revealed three distinct peaks of hemopoietic activities with different molecular sizes in the supernatant of FHC-4D2. Neutralization test with antibodies and proliferative response to interleukin-3 (IL-3)/granulocyte-macrophage colony stimulating factor (GM-CSF)-responding IC2 cells demonstrated that the hemopoietic activities were attributed to GM-CSF and macrophage colony stimulating factor (M-CSF). Transcripts of GM-CSF and M-CSF were readily detectable in Northern blot analysis, whereas no messages for IL-3, IL-6, CSF for granulocytes (G-CSF) or erythropoietin (EPO) were identified. Therefore, this is the first report on the fetal hepatocyte cell line capable of supporting hemopoiesis.