Benign preparation of aqueous core poly lactic-co-glycolic acid (PLGA) microcapsules.

Poly lactic-co-glycolic acid (PLGA) has attracted considerable attention as a polymer for drug delivery carriers. However, the hydrophobic property of PLGA often leads to the use of harmful organic solvents and poor encapsulation efficiency of hydrophilic materials. To our knowledge, a preparation method of aqueous core PLGA microcapsules without using harmful organic solvents has not been proposed. In this study, we attempted to establish an encapsulation technique of hydrophilic materials in aqueous core biodegradable and biocompatible PLGA microcapsules using vegetable oil as a continuous phase. As a result, the temperature of the oil/water mixture was required to be above the glass transition temperature. In this condition, two different types of morphology were prepared. When the water volume was below the solubility limit, PLGA microcapsules with a smooth shell were formed. In contrast, when the water volume was above the solubility limit, colloidosome-like microcapsules with PLGA nanoparticles assembled at the interface were formed. The obtained microcapsules were then heated at the glass transition temperature. The result is that aqueous core PLGA microcapsules with a smooth shell were prepared using plant oil as a continuous phase. Rhodamine B used as a hydrophilic model encapsulant, was successfully encapsulated in the PLGA microcapsules

Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells

Tumor cell invasion and metastasis are associated with the proteolytic activity of various types of proteinases. Among them, cathepsins, which are lysosomal proteinases, have received more attention recently. Since elevated expressions of cathepsins and diminished levels of their inhibitors have been observed in several human cancers, including breast, gastric and prostate cancer, especially in aggressive cancer cells, cathepsins have been suggested to be biological markers of malignant tumors and have proved useful for prognosis of the disease. Furthermore, cathepsins have various roles in cancer progression. Cathepsin D has a mitogenic activity independent of its proteolytic activity and it attenuates the anti-tumor immune response of decaying chemokines to inhibit the function of dendritic cells. Cathepsins B and L have been shown to play an important role in matrix degradation and cell invasion. The administration of their inhibitors prevents the invasion and metastasis of cancer cells. These results indicate that cancer cells orchestrate various cathepsins to progress malignant diseases. Cathepsins may be a potential target for cancer therapy

ベクロニウム・ブロマイドの薬物動態学ならびに薬力学

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1165号,学位授与年月日：平成4年3月4日,学位授与年：199

Interactive controller for audio object localization based on spatial representative vector operation

Abstract-In this paper, we propose a new interactive controller for audio object localization based on spatially representative vector operations on a stereo mixed source. First, we developed the interactive controller, which is equipped with a capacitive touchscreen panel so that the listener can intuitively operate audio objects displayed on the touchscreen panel with a touch pen. Next, we assessed the perceptual effects of localization and the sound quality of an audio object after performing individual operations to verify the operation of the interactive controller via a subjective evaluation. The results of the experiments clarify that the interactive controller enables the listener to change the gain and the localization of audio objects without sound degradation if the gain operation is not extreme

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

After a nascent chain of a membrane protein emerges from the ribosomal tunnel, the protein is integrated into the cell membrane. This process is controlled by a series of proteinaceous molecular devices, such as signal recognition particles and Sec translocons. In addition to these proteins, we discovered two endogenous components regulating membrane protein integration in the inner membrane of Escherichia coli. The integration is blocked by diacylglycerol (DAG), whereas the blocking is relieved by a glycolipid named membrane protein integrase (MPIase). Here, we investigated the influence of these integration-blocking and integration-promoting factors on the physicochemical properties of membrane lipids via solid-state NMR and fluorescence measurements. These factors did not have destructive effects on membrane morphology because the membrane maintained its lamellar structure and did not fuse in the presence of DAG and/or MPIase at their effective concentrations. We next focused on membrane flexibility. DAG did not affect the mobility of the membrane surface, whereas the sugar chain in MPIase was highly mobile and enhanced the flexibility of membrane lipid headgroups. Comparison with a synthetic MPIase analog revealed the effects of the long sugar chain on membrane properties. The acyl chain order inside the membrane was increased by DAG, whereas the increase was cancelled by the addition of MPIase. MPIase also loosened the membrane lipid packing. Focusing on the transbilayer movement, MPIase reduced the rapid flip-flop motion of DAG. On the other hand, MPIase could not compensate for the diminished lateral diffusion by DAG. These results suggest that by manipulating the membrane lipids dynamics, DAG inhibits the protein from contacting the inner membrane, whereas the flexible long sugar chain of MPIase increases the opportunity for interaction between the membrane and the protein, leading to membrane integration of the newly formed protein