Haruhiko Kondo

NECC1, a candidate choriocarcinoma suppressor gene that encodes a homeodomain consensus motif

We isolated a candidate choriocarcinoma suppressor gene from a PCR-based subtracted fragmentary cDNA library between normal placental villi and the choriocarcinoma cell line CC1. This gene comprises an open reading frame of 219 nt encoding 73 amino acids and contains a homeodomain as a consensus motif. This gene, designated NECC1 (not expressed in choriocarcinoma clone 1), is located on human chromosome 4q11-q12. NECC1 expression is ubiquitous in the brain, placenta, lung, smooth muscle, uterus, bladder, kidney, and spleen. Normal placental villi expressed NECC1, but all choriocarcinoma cell lines examined and most of the surgically removed choriocarcinoma tissue samples failed to express it. We transfected this gene into choriocarcinoma cell lines and observed remarkable alterations in cell morphology and suppression of in vivo tumorigenesis. Induction of CSH1 (chorionic somatomammotropin hormone 1) by NECC1 expression suggested differentiation of choriocarcinoma cells to syncytiotrophoblasts. Our results suggest that loss of NECC1 expression is involved in malignant conversion of placental trophoblasts.

Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene

To obtain functional evidence for DCC as a tumour suppressor associated with endometrial cancer, the human DCC cDNA encoding a complete open reading frame (ORF) was transfected into highly tumorigenic human endometrial carcinoma cells, HHUA and Ishikawa in which DCC expression was completely deleted. Reconstituted expression of DCC in HHUA had little effect on in vitro growth, but suppressed tumour formation in mice completely. The clones from Ishikawa had abundant DCC expression similar to that in normal endometrium. Their growth in vitro was suppressed and showed apoptotic phenotype. Lower levels of DCC expression in the prolonged passaged clones did not induce apoptosis, but still had the potential to suppress tumorigenicity. These observations imply a role of DCC in regulation of normal endometrial cell growth, and categorize DCC as the tumour suppressor gene for endometrial cancer.

Electrical and Photovoltaic Properties of n-Type Nanocrystalline-FeSi2/p-Type Si Heterojunctions Prepared by Facing-Targets Direct-Current Sputtering at Room Temperature

Semiconducting nanocrystalline iron disilicide (NC-FeSi2) thin films were deposited on Si(111) substrates by facing-targets direct-current sputtering at room temperature. The electrical and photovoltaic properties of the n-type NC-FeSi2/p-type Si heterojunctions were measured and investigated. We experimentally proved the possibility of employing this combination in photovoltaics. A large leakage current observed in the current–voltage characteristics, which was predominantly due to the heterojunction interface defects, resulted in a low conversion efficiency.

Newly-developed Sendai virus vector for retinal gene transfer: reduction of innate immune response via deletion of all envelope-related genes.

Recombinant Sendai virus vectors (rSeV) constitute a new class of cytoplasmic RNA vectors that have shown efficient gene transfer in various organs, including retinal tissue; however, the related immune responses remain to be overcome in view of clinical applications. We recently developed a novel rSeV from which all envelope‐related genes were deleted (rSeV/dFdMdHN) and, in the present study, assess host immune responses following retinal gene transfer.

Impact of deletion of envelope-related genes of recombinant Sendai viruses on immune responses following pulmonary gene transfer of neonatal mice

We demonstrated previously that the additive-type recombinant Sendai virus (rSeV) is highly efficient for use in pulmonary gene transfer; however, rSeV exhibits inflammatory responses. To overcome this problem, we tested newly developed non-transmissible constructs, namely, temperature-sensitive F-deleted vector, rSeV/dF (ts-rSeV/dF) and a rSeV with all the envelope-related genes deleted (rSeV/dFdMdHN), for pulmonary gene transfer in neonatal mice, by assessing their toxicity and immune responses. The gene expression in the lungs of neonatal ICR mice peaked on day 2, then gradually decreased until almost disappearing at 14 days after infection in all constructs. Loss of body weight and mortality rate, however, were dramatically improved in mice treated with SeV/dFdMdHN (mortality=0%, n=41) and ts-rSeV/dF (24.2%, n=33) compared with additive rSeV (70.7%, n=58). Although the deletion of envelope-related genes of SeV had a small impact on the production of antibody and cytotoxic T-lymphocyte activity in both adults and neonates, a dramatic reduction was found in the events related to innate responses, including the production of proinflammatory cytokines, particularly in the case of neonates. These results indicate that pulmonary gene transfer using SeV/dFdMdHN warrants further investigation for its possible use in developing safer therapeutics for neonatal lung diseases, including cystic fibrosis.

Ischemic ileal perforation in the donor of monochorionic twins complicated by twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) carries a significant risk of perinatal morbidity and mortality. Serial amnioreduction and fetoscopic laser photocoagulation have decreased perinatal mortality, thereby shifting attention towards short-term and long-term morbidity. Most morbidity occurs within the central nervous system. Ischemic lesions, however, such as congenital skin loss and limb necrosis may occur anywhere in the vasculature of recipient twins. Ischemia may also occur during serial amnioreduction and fetoscopic laser photocoagulation. We report a case of ileal perforation in the donor twin of untreated TTTS. Histopathology showed a focal area of erosion, possibly from ischemia. We also discuss the clinical features of ischemic intestinal complications of TTTS and review the literature.

Photovoltaic properties of n-Type nanocrystalline-FeSi2/intrinsic-Si/p-Type Si heterojunctions fabricated by facing-targets DC sputtering

Nanocrystalline FeSi2 (NC-FeSi2) thin films were grown on Si(111) substrates by facing-targets DC sputtering at room temperature using FeSi2 targets. The NC-FeSi2 films showed hopping conduction behavior, which was confirmed by the temperature dependence of the electric conductivity. n-Type NC-FeSi2/p-type Si and n-type NC-FeSi2/i-Si/p-type Si heterojunctions were prepared to be employed as photovoltaics. For the p-i-n heterojunctions, i-Si thin layer reduced the leakage current and improved photovoltaic properties as compared to the p-n heterojunctions. This improvement might be due to the i-Si layer that acts as a leakage blocking layer rather than a light absorption layer.