Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development

The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly.     

Determination of triazolam in serum by deactivated metal capillary gas chromatography with electron-capture detection

A method for the determination of trace amounts of triazolam in serum by deactivated metal capillary gas chromatography with electron-capture detection was established. The column used exhibits excellent thermostability in high-temperature analysis and easy handling and a long lifetime of the column and well shaped peaks on the chromatograms are obtained. With the metal capillary column, it was found to be easier to maintain suitable analytical conditions for the routine assay of triazolam than with a fused-silica column. With this method, 0.5 ng/ml of triazolam in serum can be determined. The method is useful for pharmacokinetic and therapeutic purposes.     

Optimization of cell culture conditions for production of biologically active proteins

We investigated the basic technology of cell culture conditions for production of useful substances such as cytokines, and related proteins produced by Namalwa cells. Namalwa cells (Klein, 1972), human B lymphoblastoid cells, were used for large scale production of alpha-interferon (Klein, 1979). Namalwa KJM-1, a subline of Namalwa cells, adapted to serum- and albumin-free medium, can grow at a high density above 1 × 10⁷ cells/ml in suspension mode by the use of a perfusion culture system, Biofermenter^?, containing a cone-type cell-sedimentation column as cell separator (Sato, 1983).Several kinds of cytokine cDNA can be introduced and expressed in Namalwa KJM-1 cells (Miyaji, 1990a,b,c). Some of these were produced in large quantities by use of a gene amplification method with dhfr (Miyaji, 1990c), even though the Namalwa KJM-1 cells contained endogenous dhfr genes. For stable production of the target protein, Namalwa KJM-1 cells are very useful host cells, because they have no effective endogenous protease activity in the conditioned medium.Using Biofermenter with micro-silicone fibers and a dialysis system, the specific productivity of the target proteins was not depressed at a high cell density.     

Rabbit autoantibodies to actin induced by immunization with modified homologous actins

Actin is a major antigen involved in the reaction of smooth muscle antibody positive sera from patients with chronic active hepatitis. In the present study, actin extracted from rabbit skeletal muscle was denatured by sodium dodecyl sulfate and was immunized into the rabbit, a homologous animal for actin. The rabbits, thus immunized, produced antibodies reactive with actins of homologous and heterologous animals. In addition, the antibodies showed reactivity with autologous actin. It indicates that the denatured homologous actin is capable of terminating immunological tolerance to actin and induces formation of autoantibody to rabbit actin. This phenomenon may be implicated in the occurrence of anti-actin antibody in sera from patients with chronic liver disease and several other diseases.     

The C-Terminal Region of Rift Valley Fever Virus NSm Protein Targets the Protein to the Mitochondrial Outer Membrane and Exerts Antiapoptotic Function

The NSm nonstructural protein of Rift Valley fever virus (family Bunyaviridae, genus Phlebovirus) has an antiapoptotic function and affects viral pathogenesis. We found that NSm integrates into the mitochondrial outer membrane and that the protein''s N terminus is exposed to the cytoplasm. The C-terminal region of NSm, which contains a basic amino acid cluster and a putative transmembrane domain, targeted the protein to the mitochondrial outer membrane and exerted antiapoptotic function.     

Protective effects of sodium selenite on killing and mutation by N-methyl-N''-nitro-N-nitrosoguanidine in E. coli.

Sodium selenite was found to protect Escherichia coli cells against killing and mutagenic effects of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Such protective effects were not observed when cells were treated with N-methyl-N-nitrosourea (MNU). The protection by sodium selenite was not controlled by the ada gene, which is responsible for the repair of alkylated damage in DNA. A reduction of the amount of glutathione was found when cells were treated with sodium selenite, and glutathione is known to be involved in the methylation of DNA by MNNG, not by MNU. Reduced methylation by MNNG due to the reduction of the amount of glutathione caused by abundant sodium selenite was suggested to be the mechanism of protection.     

7-O-Galloyl-(+)-catechin and 3-O-galloylprocyanidin B-3 from Sanguisorba officinalis

7-O-Galloyl-(+)-catechin and 3-O-galloylprocyanidin B-3, along with gambiriins A-1 and B-3 and four polygalloylglucoses, have been isolated fro     

4′,6-Dimethoxyisoflavone-7-<Emphasis Type="Italic">O</Emphasis>-β-<Emphasis Type="SmallCaps">d</Emphasis>-glucopyranoside (wistin) is a peroxisome proliferator-activated receptor α (PPARα) agonist in mouse hepatocytes

Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases. We found that vanillin binds strongly to the active site cavity of CAMKIV and stabilized by a large number of non-covalent interactions. We explored the utility of vanillin as anti-cancer agent and found that it inhibits the proliferation of human hepatocyte carcinoma (HepG2) and neuroblastoma (SH-SY5Y) cells in a dose-dependent manner. Furthermore, vanillin treatment resulted into the significant reduction in the mitochondrial membrane depolarization and ROS production that eventually leads to apoptosis in HepG2 and SH-SY5Y cancer cells. These findings may offer a novel therapeutic approach by targeting the CAMKIV using natural product and its derivative with a minimal side effect.