Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids

Adult T-cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T-cell leukaemia virus type I (HTLV-I) infected T-cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV-I-infected T-cell lines was significantly reduced within 72 h by 1.0 micromol/l As2O3. Growth of two out of four HTLV-I-infected T-cell lines was also inhibited by 1.0 micromol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by AS2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 micromol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.     

Kinetic studies on the removal of extracellular hydrogen peroxide by cultured fibroblasts

To investigate the function of antioxidant enzymes in intact cells, we examined the removal of extracellular H2O2 by cultured fibroblasts (IMR-90). H2O2 concentration dependence of the reaction rate was interpreted as that the process involves two kinetically different reactions (referred to as reactions 1 and 2). Reaction 1 was characterized by a relatively low Km value (about 40 microM), and reaction 2 by linear dependence of the rate up to 500 microM H2O2. The magnitude of reaction 1 was reduced by treatment of the cells with diethyl maleate or 6-amino-nicotinamide, while reaction 2 was inhibited by 3-amino-1,2,4-triazole treatment. It was concluded that reactions 1 and 2 are principally due to GSH peroxidase and catalase, respectively. The values of kinetic parameters were estimated by curve-fitting, and it was inferred that 80 to 90% of H2O2 is decomposed by GSH peroxidase at H2O2 concentrations lower than 10 microM. The contribution of catalase increases with the increase in H2O2 concentration. The intact cells showed a low catalase activity (about 15%), as compared with the activity found in the solubilized cells. The low catalase activity was ascribed to the latency of the enzyme caused by localization in peroxisomes. Fibroblasts also removed intracellular H2O2 generated by menadione. Treatment with diethyl maleate greatly impaired the H2O2-removing capability and caused H2O2 efflux into the medium.     

Increased expression of endothelial cell nitric oxide synthase (ecNOS) in afferent and glomerular endothelial cells is involved in glomerular hyperfiltration of diabetic nephropathy

Root coverage procedures have become an important part of periodontal therapy. The purpose of this study was to compare 2 techniques, 1) guided tissue regeneration (GTR) with a bioabsorbable polylactic acid softened with citric acid ester membrane and 2) the connective tissue graft combined with a coronally positioned pedicle graft without vertical incisions. The GTR procedure produced a mean root coverage of 92.3% and the connective tissue graft combined with a coronally positioned pedicle graft, 95.0%. This difference was not statistically significant. Both procedures produced similar reductions in recession depth, recession width, and probing depth. The connective tissue graft combined with a coronally positioned pedicle graft resulted in a greater increase in the amount of keratinized tissue. Based on this study, both procedures can result in statistically similar amounts of mean root coverage, but the results are not identical. In most cases, the connective tissue with coronally positioned pedicle graft produced a more bulky result than guided tissue regeneration. Therefore, the procedures are not interchangeable.     

Host genes affecting survival period of chemically induced bladder cancer in mice

Treatment of C57BL/6 J (B6) and NON male mice with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) resulted in a high incidence of bladder cancer. The mean survival period, however, differed significantly by strain: 481+/-219 days in B6 (n = 31) and 203+/-119 days in NON (n = 30) (P < 0.0001). Major causes of death were renal failure due to obstruction of the urinary tract, or local invasion of tumors. The fact that the BBN-treated NON x B6 reciprocal F1 mice had survival periods as short as those of the parental NON mice suggests a genetically dominant susceptibility in NON or recessive resistance in B6. A linkage analysis of 248 back-cross mice to B6 suggested at least two quantitative trait loci determining the length of the survival period: one was mapped close to D2Mit260 (logarithm of odds, LOD, score 2.21), a microsatellite marker locus 83 cM from the centromere on chromosome 2, and another was close to D6Mit159, 7 cM from the centromere on chromosome 6 (LOD score 2.51).     

Phenotypes and invariant alpha beta TCR expression of peripheral V alpha 14+ NK T cells

A novel subset of peripheral T cells, peripheral NK T cells, is found to be a major population comprising 5% of splenic T and 40% of bone marrow T cells. The majority of peripheral NK T cells are characterized by the expression of an invariant TCR-alpha encoded by V alpha 14/J alpha 281 with a one nucleotide N region. Moreover, a specific reduction of V alpha 14+ NK T cells has been demonstrated to be tightly associated with various autoimmune diseases, indicating their decisive role in autoimmune disease development. In this study, we investigated the phenotypes of peripheral V alpha 14+ NK T cells and their TCR-beta repertoire. Peripheral V alpha 14+ NK T cells, comprise two populations, i.e., small and large sized cells, at an equal frequency, belonged to the CD4- CD8- fraction, and are heat stable antigen(bright), macrophage-1bright, B220bright, CD45RBdim, and Mel-14dim, but CD5-, distinct from thymic NK T cells. TCR-beta analysis clearly showed that peripheral V alpha 14+ NK T cells utilized two to three dominant invariant TCR-beta, such as V beta 8.2 D beta J beta 2.5/V beta 7 D beta J beta 2.1 in the spleen and liver, V beta 8.2 D beta J beta 2.5/V beta 8.3 D beta J beta 2.2/V beta 7 D beta J beta 2.6 in the bone marrow, and V beta 7 D beta J beta 2.1/V beta 3 D beta J beta 1.2 in intestinal intraepithelial lymphocytes. Judging from the unusual surface phenotypes, such as heat stable antigen, macrophage-1, B220, CD45RBdim, and Mel-14dim, which are known to be T cell activation markers, peripheral V alpha 14+ NK T cells may always be activated under physiologic conditions, resulting in the oligoclonal expansion of V alpha 14+ NK T cells with different invariant TCR-beta in different peripheral organs. The unique features of V alpha 14+ NK T cells are discussed.     

Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein

We have cloned a cDNA for a novel human homolog of the Drosophila discs large (dig) tumor suppressor protein, termed NE-dlg (neuronal and endocrine dig). Northern blot analysis revealed that the gene is highly expressed in neuronal and endocrine tissues. Fluorescence in situ hybridization (FISH) and radiation hybrid mapping studies localized the NE-dlg gene to chromosome Xq13. We also found that the NE-dlg gene encoded a 100 kDa protein. Immunolocalization studies using an NE-dlg antibody showed that the protein tended to be expressed in non-proliferating cells, such as neurons, cells in Langerhans islets of the pancreas, myocytes of the heart muscles, and the prickle and functional layer cells of the esophageal epithelium. Proliferative cells, including various cultured cancer cell lines and basal cells in the esophageal epithelium, showed little expression of the NE-dlg protein. In addition, yeast two-hybrid screening and in vitro binding assays revealed that the NE-dlg interacted with the carboxyl-terminal region of the APC tumor suppressor protein. These data suggest that NE-dlg negatively regulates cell proliferation through its interaction with the APC protein.     

Repeated temperature modulation epitaxy for p-type doping and light-emitting diode based on ZnO.

Since the successful demonstration of a blue light-emitting diode (LED), potential materials for making short-wavelength LEDs and diode lasers have been attracting increasing interest as the demands for display, illumination and information storage grow. Zinc oxide has substantial advantages including large exciton binding energy, as demonstrated by efficient excitonic lasing on optical excitation. Several groups have postulated the use of p-type ZnO doped with nitrogen, arsenic or phosphorus, and even p-n junctions. However, the choice of dopant and growth technique remains controversial and the reliability of p-type ZnO is still under debate. If ZnO is ever to produce long-lasting and robust devices, the quality of epitaxial layers has to be improved as has been the protocol in other compound semiconductors. Here we report high-quality undoped films with electron mobility exceeding that in the bulk. We have used a new technique to fabricate p-type ZnO reproducibly. Violet electroluminescence from homostructural p-i-n junctions is demonstrated at room-temperature.     

Analysis of graded-index polymer optical fiber link performance under fiber bending

Bending effects on bandwidth and loss of a graded-index polymer optical fiber (GI POF) were investigated, and those influences on the optical link performance were discussed simultaneously for the first time. The numerical apertures (NAs) of the GI POFs were deliberately varied from 0.154 to 0.292. A bending radius larger than 10 mm induced little mode coupling and little change in the bandwidth of the GI POF. A bending radius smaller than 10 mm caused degradation in the bandwidths of the higher NA GI POFs. On the other hand, in the lower NA GI POFs, even more severe bending could cause little change in their bandwidths. Thus, the lower NA GI POF seemed preferable in suppressing the bandwidth change. However, the higher NA GI POF exhibited the lower bending loss. The preferable NAs for both characteristics were completely opposite. Moreover, the bending loss under underfilled launch (UFL) could be lower than that under overfilled launch (OFL). On the other hand, the bending loss was equivalent to the bandwidth degradation in view of the link power penalty. Therefore, the bandwidth change and loss caused by the bending were the critical factors to optimize the optical link considering the link power budget. The high-NA GI POF with almost ideal refractive-index profile could provide stable high performance in overgigabit communication even under any bending conditions.     

Activity tests of various catalysts for hydrocracking of coal by means of high pressure differential thermal analysis

The activities of fourteen kinds of catalysts for the hydrocracking of Taiheiyo coal were examined by a high pressure differential thermal analytical method. Exothermic peaks appeared at low temperatures (420–430°C) when MoO₃TiO₂, NiY zeolite and CoY zeolite were used as catalysts, indicating that these catalysts are highly active compared with other catalysts including MoO₃CoOAl₂O₃. The qualitative analysis of gas and liquid products revealed that MoO₃TiO₂ and CoY are good catalysts for the liquefaction reaction. The hydrogenation ability of the catalyst is concluded to be more important than its acidic property.