This review focuses on the structure and function of the biological membranes. It was prepared for researchers working on artificial membranes. The table of contents is as follows ; (1) Introduction. (2) Structure of the biological membrane ; 1) The cell is a living unit. 2) The biological membrane is represented as the fluid mosaic model. 3) The membrane lipids are amphipathic. 4) The lipid molecules form micelles or bimolecular sheets in aqueous envionments. 5) The lipid molecules diffuse within the lipid bilayer. 6) The lipids distribute asymmetrically in the biological membrane. 7) The proteins distribute asymmetrically in the biological membrane. (3) Functions of the biological membrane ; 1) The biological membrane has multiple functions. 2) The lipid bilayer is a barrier. 3) The ion composition is different between inside and outside the cell. 4) Transports across the membrane are either energy dependent or independent. 5) The lipid bilayer limits the transfer of the polar molecules. 6) Gate regulates ion-channel. 7) The rate of facilitated diffusion is limited. 8) The active transport needs energy. 9) P-type pump is phosphorylated. 10) The secretion and absorption accompany dynamic cytosis. 11) The information is transmitted through the membrane. 12) The membrane skeleton is important. 13) The erythrocyte deforms. 14) The membrane skeleton is ubiquitous. 15) The enzyme reaction in the membrane obeys a Michaelis-Menten equation. 16) The analysis of membrane disorder would reveral normal membrane functions. (4) Conclusion.

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Movements of transferrin and α₂-macroglobulin receptor molecules in the plasma membrane of cultured normal rat kidney (NRK) fibroblastic cells were investigated by video-enhanced optical microscopy with 1.8 nm spatial precision and 33 ms temporal resolution by labeling the receptors with the ligand-coated nanometer-sized colloidal gold particles. For both receptor species, approximately 90% of the movement trajectories are of the confined diffusion type, within domains of=0.25 μm² (500-700 nm in diagonal length). Movement within the domains is random with a microscopic diffusion coeffcient (D_micro) =10_-9cm²/s, which is consistent with that expected for free Brownian diffusion of proteins in the plasma membrane. The receptor molecules move from one domain to one of the adjacent domains at an average frequency of 0.034s^-1 (the residence time within a domain=29s), indicating that the plasma membrane is compartmentalized for diffusion of membrane receptors and that longrange diffusion is the result of successive intercompartmental jumps. The macroscopic diffusion coefficients for these two receptor molecules calculated on the basis of the compartment size and the intercompartmental jump rate are=2.4 × 10^-11cm²/s, which is consistent with those determimed determined by averaging the long-term movements of many particles. Partial destruction of the cytoskeleton decreased the confined diffusion mode, increased the simpple diffusion mode, and induced the directed diffusion (transport) mode, Those resules suggest that the boundaries between compartments are made of dynamically fluctuating membrane skeletons (membrane-skeletion fence model).
The mechanical properties of intercompartmental boundaries were then studied by tagging transferrin receptor (TR) with either 210 nm-φ latex or 40nm-φ colloidal gold particles, and by dragging the particle-TR complexes laterally along the plasma membrane using laser tweezers. Approximately 90% of the TR-particle complexes that showed confined-type diffusion with D_micro of=10^-9cm²/s could be dragged past the intercompartmental boundaries in their path by laser tweezers at a trapping force of 0.35-0.8 pN. At the dragging forces between 0.05 and 0.1 pN, particle-TR complexes tended to escape from the laser trap at the boundaries, and such escape occurred in both the forward and backward directions of dragging. The average distance dragged was half of the confined distance of TR, which further indicates that particle-TR complexes escape at the compartment boundaries. The boundaries are likely present in the cytoplasmic domain, and are elastic. These results are consistent with the proposal that the compartment boundaries consist of membrane skeleton or a membrane-associated part of the cytoskeleton. Approximately 10% or TR exhibited slower diffusion (D_micro=10^-10-10^-11cm²/s) and binding to elastic structures.

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Protein tyrosine phosphorylation of numerous proteins have been observed by many during platelet activation processes. Especially, the relation between protein tyrosine phosphorylation and platelet aggregation or adhesion has been extensively studied. In view of the recent progresses achieved in many laboratories including ours, we would like to present a comprehensive review on this ever growing field.

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To investigate which regions of the Na, K-ATPase β subunit are required for the functional αβ complex formation of the Na, K-ATPase, we constructed chimeric β subunits between the Na, K-and the H, K-ATPase β subunits, and expressed in Xenopus oocytes together with the Na, K-ATPase α subunit. The chimera, that was composed of N-terminal cytoplasmic region of the H, K-ATPase β subunit combined with transmembrane and extracellular region of the Na, K-ATPase β subunit, formed a functional enzyme with the Na, K-ATPase α subunit. This means that N-terminal cytoplasmic region of the β subunit is interchangeable between the Na, K-and H, K-ATPases. The chimeras, whose C-terminal extracellular domain was derived from H, K-ATPase β subunit, formed inactive enzyme in ATPase activity, suggesting that the extracellular domain was essential for the functional expression of the Na, K-ATPase.
The Cys127-Cysl50 disulfide-bonded loop (L₁) located within the extracellular domain of the Na, K-ATPase β subunit was substituted with the corresponding loop of pig H, K-ATPase β subunit. The complex of the α subunit with this mutant β subunit was inactive in ATP hydrolysis. Phe148 within the L₁ of the pig H, K-ATPase β subunit-substituted mutant were back-mutated to Arg148. This mutation restored the ability of the mutant β subunit to form a functional complex with the α subunit. These results suggested that the Cys127-Cys150 loop of the Na, K-ATPase β subunit, especially Arg148, plays a critical role in the functional expression of the Na, K-ATPase.

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The separation process of various molecules in inorganic membranes was investigated by using molecular dynamics, quantum chemical calculation, and computer graphics. It was indicated that an inorganic membrane with the high selective affinity to CO₂ molecules is effective and efficient to separate CO₂ molecules from the industrial exhaust gas even at high temperatures. The affinity of various membranes to CO₂ and N₂ molecules was quantitatively evaluated by quantum chemical calculations. The separation mechanism of water and various alcohol, such as methanol, ethanol, 1-propanol, and 2-propanol, in zeolite membranes was suggested. Moreover, the applicability of carbon nanotubes for the separation of organic molecules, such as 2, 6-dimetyl naphthalene and 2, 7-dimetyl naphthalene was also demonstrated.

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We intended to elucidate the mechanism of virus removal by cuprammonium regenerated cellulose hollow fiber (BMM^TM). The removability of viruses with various sizes was examined as a function of the mean pore size of BMM and the population distribution of virus captured in BMM was evaluated through electron microscopy. The removability of viruses was dependent on their sizes and the viruses caught in the membrane distributed in void pore stepwise along the filtration direction. The virus removability decreases with an increase in the concentration of coexisting protein and with an increase in the filtration volume. The changes in the virus removability due to the changes in the filtration condition could be interpreted through the pore structure change caused by the filtration and the contribution of plugging in the capillary pore and trapping in the void pore. It was found that the BMM filtered viruses through multi-step filtration. We conclude that mechanism of the virus removal is the sieving effect and thus, the removability of viruses can be predicted from their sizes using the proposed empirical relationship.

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Vapor-permeation (VP) aided esterification of oleic acid with ethanol and methanol was carried out at 383 K using both a pressurized vapor circulation system and a laboratory module of Zeolite membrane with excellent VP performance of dehydration of organic liquids. The combined process provided almost complete conversion in a short reaction time with the initial molar ratio of alcohol to oleic acid (m₀) of 1.5. The reaction time, as for ethanol, was reduced by a factor of 1/3 as compared with the process carried out under the atmospheric pressure using a laboratory module of polyimide hollow fiber. The loss of alcohol by permeation was below 0.01% of the feed for ethanol and was only 0.16% for methanol. This indicates that the almost complete reaction can be achieved even if m₀ goes down to unity. The Zeolite membrane worked effectively and stably for a long period, and is useful for achieving the highly efficient process of esterification.

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A monolithic microcapsule-depot form using a biodegradable polymer was designed and developed, which constantly releases a super-active agonist of LH-RH, leuprorelin, at a constant rate for about one month following a single injection. Microcapsules containing the drug were prepared by a new preparation technique, modifying the solvent evaporation method. When copoly (lactic/glycolic) acid of copolymer ratio of 75/25 and average molecular weight of 10, 000 was adopted a biodegradable polymer, leuprorelin was eliminated from the injection site in rats at a pseudo-zero order rate for one month after a single subcutaneous or intramuscular injection of the microcapsules. Serum leuprorelin levels were maintained at a steady level in rats and dogs for 4 weeks after an injection, and serum testosterone levels decreased to below the normal level and were maintained at the suppressed level for more than 6 weeks. The results indicate that the microcapsule dosage form is useful for LH-RH therapy of sex hormone dependent diseases.
After extended clinical evaluation, the monthly microcapsule-depot form of leuprorelin for treating prostate cancer, endometriosis, precocious puberty, and other sex hormone dependent diseases was approved by health authorities in U.S.A., Europe, and Japan as Lupron^®; Depot, Enantone^®; Depot, and Leuprin^®;, respectively.

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