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Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in vivo has been a challenging task. In an effort to overcome this long-standing problem, we selected interferon-β and examined its synthesis. The 166 residue polypeptide chain of interferon-β was prepared by covalent condensation of two synthetic peptide segments and a glycosylated synthetic peptide bearing a complex-type glycan of biological origin. The peptides were covalently condensed by native chemical ligation. Selective desulfurization followed by deprotection of the two Cys(Acm) residues gave the target full-length polypeptide chain of interferon-β bearing either a complex-type sialyl biantennary oligosaccharide or its asialo form. Subsequent folding with concomitant formation of the native disulfide bond afforded correctly folded homogeneous glycosyl-interferon-β. The chemically synthesized sialyl interferon-β exhibited potent antitumor activity in vivo.

We propose and demonstrate the "defect-induced plasma process" for the fabrication of the room-temperature-operated carbon nanotube single-electron transistors (CNT-SETs) with the SiO2 protection films on the CNT channels. After introducing of defects in the CNT channels by O2 plasma irradiation through the SiO2 protection films, multi-quantum dots were fabricated in the CNT channels. The electrical properties of the CNT-SETs suggested that the oscillation in the drain currents as a function of the gate voltage was observed at room temperature, as a result of the Coulomb blockade effect. Moreover, we report that the yield of the CNT-SETs depended on the thickness of the SiO2 protection films on the CNT channels for the purpose of obtaining a high yield of CNT-SETs. The results indicate that the high yield of the CNT-SETs is as high as approximately 35% when the SiO2 protection film thickness is 60 nm. Consequently, the defect-induced plasma process is useful for obtaining the high yield efficiency of CNT-SETs operating at room temperature.

Using the patterned chemical catalyst, the position of the carbon nanotube was successfully controlled. Using this carbon nanotube as a channel, the single electron transistor was fabricated. The defects in the carbon nanotube formed spontaneously quantum dots with the size of ~1 nm. The single electron transistor showed the room-temperature Coulomb diamond characteristics with an ultra-high Coulomb energy of 5000 K.

The solubility, diffusivity, and permselectivity of propylene and propane in 40 different polyimides synthesized from 2,2-bis(3,4-decarboxyphenyl)hexafluoropropane dianhydride (6FDA) were determined at 298 K. The influence of the chemical structures on the physical and gas permeation properties of the 6FDA-based polyimides was studied. The solubility of propylene in an unrelaxed volume of a polymer matrix mainly contributes to the total solubility of propylene for various 6FDA-based polyimides. The diffusivity, the permeability of propylene, and the permselectivity in the propylene/propane mixed-gas system depend on the solubility of propylene. This is thought to be associated with the penetrant-induced plasticization effect. 6FDA-based polyimides, which have a high glass-transition temperature and a large fractional free volume, exhibit a high permeability with a relatively low permselectivity. Changing the number of-CH3 substituents in the phenylene linkage and changing the connectivity in the main chain are good ways of controlling the solubility of propylene and the corresponding permselectivity in the propylene/propane mixed-gas system. Some 6FDA-based polyimides restrict the solubility of propylene through the introduction of a -CONH- linkage between the phenylene linkage; the -Cl substituent in the phenylene linkage at the diamine moiety exhibits a high separation performance in the mixed-gas system. The polyimides are potentially useful membrane materials for the separation of propylene and propane in the petrochemical industry.

The solubility, diffusivity, and permselectivity of 1,3-butadiene and n-butane in seven different polyimides synthesized from 2,2-bis (3,4-carboxyphenyl) hexafluoropropane dianhydride (6FDA) were determined at 298 K. The influence of chemical structures on physical and gas permeation properties of 6FDA-based polyimides was studied. Solubility of 1,3-butadiene in 6FDA-based polyimides can be described by a dual-mode sorption model. 1,3-Butadiene-induced plasticization is considered to be associated with the increasing permeabilities of 1,3-butadiene and n-butane and the decreasing permselectivity of 1,3-butadiene vs. n-butane in the mixed gas system containing a high concentration of 1,3-butadiene. It was found that controlling the solubility of 1,3-butadiene in an unrelaxed volume in 6FDA-based polyimides is very important to maintain the high permselectivity of 1,3-butadiene vs. n-butane in the mixed gas system. Changing the-C(CF 3 ) 2 - linkage to a -CH 2 -, -O- linkage, removing methyl substituents at the ortho position of the imide linkage, and changing the p-phenylene linkage to an m-phenylene linkage in the main chains in some 6FDA-based polyimides are effective to decrease fractional free volume and restrict the solubility of 1,3-butadiene in the unrelaxed volume of a polymer matrix. The 6FDA-based polyimides restricting the solubility of 1,3-butadiene in an unrelaxed volume exhibit high separation performance in the 1,3-butadiene/n-butane mixed gas system compared with conventional glassy polymers and, therefore, are potentially useful membrane materials for the separation of 1,3-butadiene and n-butane in the petrochemical industry.

The new fabrication process for a carbon nanotube (CNT) single-electron transistor (SET) operated at room temperature was proposed using La(NO3)3. The carbon nanotube reacts with oxygen included in La(NO3)3 at high temperature and the defects that worked as tunnel junctions were introduced. For consistency CNT-SET shows Coulomb oscillation and Coulomb diamond characteristics at 300 K. From the simulation, it was found that the newly proposed process introduced three effective defects into CNT, and CNT-SET worked as two islands SET.

Background —Heart failure is associated with activation of the sympathetic nervous system and downregulation of β-receptors. However, the coupling between cardiac sympathetic neuronal function and the β-receptor during the development of hypertensive heart failure is not clear. Methods and Results —We determined cardiac neuronal function and β-receptors with a dual-tracer method of [ 131 I]metaiodobenzylguanidine (MIBG) and 125 I-cyanopindolol (ICYP) in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12 weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE) content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes decreased, by 52% and 39%, respectively, in association with 71% reduction of cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was lower in the LV endocardial regions at 18 weeks in DS rats. Conclusions —The present results indicate that cardiac sympathetic neuronal function is relatively preserved at the compensated, hypertrophic stage of DS rats but deteriorates in association with β-receptor downregulation at the failing stage. The cardiac neuronal dysfunction occurs heterogeneously. A combination of scintigraphic portrayal of β-receptors with MIBG should provide valuable information regarding sympathetic nerve signaling in living hearts.

The prognosis of pancreatic adenocarcinoma still remains poor because of the lack of reliable diagnostic tests for early stages of the disease. Monoclonal antibody 17-1A (MoAb 17-1A) has been studied extensively, and the antigen recognized by MoAb 17-1A is expressed by adenocarcinomas of the pancreas and stomach, as well as other normal and malignant epithelial tissues. The potential of MoAb 17-1A was investigated for its ability to detect pancreatic carcinomas. The use of MoAb 17-1A in treatment also was studied.Immunoreactivity of MoAb 17-1A with human pancreatic carcinoma cell line HuP-T4 was examined histochemically by the avidin-biotinylated enzyme complex method. MoAb 17-1A was labeled with 125I by the Iodogen method and 111In using either diethylenetriaminepentaacetic anhydride (cDTPA) or 1-(p-benzyldiazonium) diethylenetriaminepentaacetic acid (aDTPA). After injection in nude mice bearing HuP-T4 xenografts, the biodistribution of 111In- and 125I-labeled MoAb 17-1A was examined at various time points.Positive staining of MoAb 17-1A was noted for HuP-T4 cells. A statistically significant (P0.01) greater tumor uptake was observed at 3 days after intravenous injection of 125I-labeled MoAb 17-1A when compared with 125I-labeled nonspecific immunoglobulin G. 125I- and 111In-labeled MoAb 17-1A was concentrated in HuP-T4 carcinoma 1.9-4.8 times higher than in the spleen, heart, liver, and pancreas.MoAb 17-1A was found to bind selectively to human pancreatic carcinoma HuP-T4. Tumor exhibited higher uptake of radiolabeled MoAb 17-1A compared with adjacent normal tissues. These results suggest that MoAb 17-1A may be applicable to the radioimmunodetection and radioimmunotherapy of pancreatic adenocarcinomas.

A costimulatory signal is required for the full activation of T cells, in addition to the antigen-specific signal via the T cell receptor. The inducible costimulator, ICOS is one of the costimulatory molecules that play an essential role in this process, particularly in the expansion or the development of effector T cells. As blocking of the interaction between ICOS and its ligand, B7RP-1, suppresses the T cell response, it can be applied to the treatment of allograft rejection or autoimmune diseases. Here, we isolated four scFv clones that were specific to human B7RP-1 by biopanning a human antibody phage library. We found that three of these clones inhibited the interaction between ICOS-Fc and B7RP-1-Fc. These inhibitory clones not only recognized B7RP-1 molecules expressed on B cells, as assessed by FACS, but also exhibited inhibitory activity in a proliferation assay of T cells stimulated with anti-CD3 mAb and B7RP-1-Fc. Finally, the suppression effect of the scFv on the allogenic immune response was examined using a mixed lymphocyte reaction assay, which demonstrated a successful inhibition of the allogenic reaction, in spite of the high dose needed for complete inhibition (360 nM).

We have developed In-111 labeled activated carbon microspheres (111In-CH44) for use in mammary lymphoscintigraphy and analysis of mammary lymph flow. 111In-CH44 was made by the NaI complex method. In 14 patients with breast cancer studied by double isotope method using 111In-CH44 and 99mTc-CH44 which we devoloped formerly. About 1 ml (11.1MBq, 0.3mCi) of 111In-CH44 was injected before operation into the outer side of the mammary gland, and 1 ml (74MBq, 2mCi) of 99mTc-CH44 inner side. The axillary and parasternal lymph nodes were visualized clearly using two isotopes at the same time and radioactivity of each isotope in surgically dissected lymph nodes was counted. In 8 patients with parasternal lymph nodes dissection, mean distribution of radioactivity of, respectively, 111In-CH44 and 99mTC-CH44 in each regional lymph node group was as follows : brachial and subscapular 2.3% and 0.5% : central, pectoral and subpectral 79.1% and 72.9% : interpectoral 0% and 1.8% : infraclavicular 1.9% and 5.7% : highest infraclavicular 0.4% and 0% : and parasternal 16.3% and 19.1%. Thus mammary lymph flow in the same patient can be evaluated using two isotopes at the same time. These results suggest that double isotope method using 111In-CH44 and 99mTc-CH44 is useful for the detailed analysis of mammary lymph flow.

We successfully fabricated single electron transistors (SETs) operating at room temperature with carbon nanotube (CNT) channel having different island sizes. The fabrication of the CNT SETs is performed by electrical manipulation using non-contact mode atomic force microscope (AFM). We carried out cutting or nicking of CNTs by applying negative voltage between a metal-coated AFM tip and CNT. A precise control over the CNT dot size was achieved by changing the nicking distance and CNT SETs with a dot size of 15 and 22 nm were fabricated. By changing the size of the dot we could arbitrarily change the operation characteristics of the device where the period of oscillations increases as the dot size decreases.

The absorption, distribution and excretion of butylidenephthalide after dermal application to hairless mouse have been examined with [8-14C]butylidenephthalide. By the investigation of the whole body autoradiogram and liquid scintillation analysis, it was indicated that the transdermally applied butylidenephthalide quickly permeate into peripheral circulation system without accumulation in the skin and then distribute into lung, liver, bile and kidney. The total radioactivity, however, was decreased due to excretion into urine, and in the case of i.v.-administration, 80% of the administered butylidenephthalide was excreted into urine within 24 h, while only 5% was excreted into feces within 24 h. Then, the metabolite in urine was determined to be a cysteine conjugate by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Thus, it has been concluded that after dermal application butylidenephthalide quickly permeates through skin into peripheral circulation system; distributes to lung, liver, bile and kidney; and then excreted into urine as a cysteine adduct.

The authors have succeeded in precisely controlling the exact number of individual bridging carbon nanotubes (CNTs) between two electrodes during thermal chemical vapor deposition (CVD) by counting the number of steps in a monitoring current. A direct current bias was applied between electrodes and the resulting current was monitored during the CVD process. The monitoring current showed several steplike increases, each of which corresponded to bridging by a single CNT. After thermal CVD, the number of bridging CNTs was confirmed by scanning electron microscopy observation and by the electrical breakdown process: the results coincided exactly with the number of current steps monitored during the CVD growth.

The control of the growth direction of a carbon nanotube was accomplished by applying an electric field during the growth of the carbon nanotube. The effects of two types of applied bias, one is a constant DC bias, and the other is a ramp bias, on the control of the growth direction were examined. By maintaining a constant DC bias we could control the growth direction of the carbon nanotube, however, the bridging ratio between the two electrodes was as small as 35%. We suppose that this low bridging ratio may be caused by the etching effect of hydrogen. When a ramp bias was applied, bridging ratio tended to increase with the slope of ramp bias. Under optimal conditions, the bridging ratio reached a value as high as 95%.

We demonstrate that a non-contact atomic force microscope (AFM) can be used to cut and nick carbon nanotubes (CNTs) by applying negative bias to the metal-coated AFM tip when it is very close to the CNT. The voltage needed to cut the CNT completely varied from -8 to -15 V, while the nicking voltage ranged from -6 to -8 V. This technique was applied to make a nanoscale single CNT device. Unwanted CNTs were cut first to leave only one CNT connecting the electrodes. Finally, tunneling barriers defined by two small nicks were created on the CNT to fabricate a single electron transistor. The final device shows Coulomb oscillation and Coulomb diamond characteristics at room temperature.

The effect of the selective adsorption of pig serum albumin as an antigen on the electrical properties of a carbon nanotube channel field effect transistor on which anti-pig serum albumin was immobilized as an antibody by physisorption in phosphate buffer solution has been investigated. We have succeeded in real-time detection of the adsorption of pig serum albumin on anti-pig serum albumin as a decrease in the conductance of the carbon nanotube channel field effect transistor, by a label-free process.

The air stable n-type carbon nanotube channel filed effect transistor (CNT-FET) with the top gate structure was successfully fabricated using the silicon nitride gate insulator deposited by the thermal chemical vapor deposition. The effects of the silicon nitride insulator on the electrical properties of the CNT-FET have been investigated. The p-type characteristics of the CNT-FET can be converted to the n-type characteristics in high yield of 90% only by depositing the silicon nitride insulator. The drain current is as high as few µA order. The n-type top gate CNT-FET stably operated even in ambient air.

We have succeeded in observing the single hole transistor characteristics in position-controlled grown carbon nanotubes (CNTs) with artificial defects formed by a chemical process. Coulomb blockade characteristics were observed around the hole depletion region even at room temperature. At a low temperature, however, the Coulomb blockade characteristics were observed both in hole and electron transport regions.

As prophylactic therapy of gastrointestinal carcinomas, we have made a study of immunotherapy with the liver regarded as local. An attempt was made to administer OK-432 emulsified with medium chain tryglyceride in order to increase transfer of the drug to the portal vein and target the liver by means of oral administration. Oral medication allows repeated administration and long-term treatment. The result of experiment using RI(14C-OK-432) showed that 14C-OK-432 levels in portal blood was higher by oral adminstration of OK-432-MCT emulsion than OK-432 solution. With regard to internal organ distribution, higher levels in the liver were presumed. The study on experimental hepatic metastasis, the group administered OK-432-MCT emulsion showed the most excellent inhibit effect of experimental hepatic metastasis as compared with the control group and OK-432 solution group.

To compare accumulation of the 125I-labeled antibodies (anti-carcinoembryonic antigen (CEA) monoclonal antibody and polyclonal antibody) to a CEA-producing tumor (SC-2-JCK), an in vivo localization study was performed in nude mice. The tumor-to-blood ratio at 120 hours after injection rose to 4.6 for the monoclonal antibody, but remained at 1.3 for the polyclonal antibody. However, no differences were noted between the antibodies up to 72 hours after injection. In autoradiograms, selective accumulation of the tracer was noted in the tumor for both antibodies. However, no superiority or inferiority of imaging for either of the antibodies could be definitely determined.

消化器悪性腫瘍の肝転移再発に対する予防的な治療を目的としてOK-432を中鎖脂肪でエマルジョン化して経口投与し, その効果を実験的, 臨床的に検討した. 腫瘍細胞AH60Cを用いたラットの肝転移実験において, OK-432中鎖脂肪エマルジョン経口投与群の転移抑制率は57.1%で, 無処置群との間に有意差を認めた. 細胞障害活性試験ではOK-432中鎖脂肪エマルジョン経口投与群は, 腸間膜リンパ節43%, 脾細胞50%, で水溶液投与群より高い傾向にあった. 臨床例ではOK・432中鎖脂肪エマルジョン経口投与によりNK活性の低い担癌患者5例中3例が正常値に復した. またOKT4/OKT8比が上昇した. 以上より, OK・432中鎖脂肪エマルジョン経口投与の有用性が示唆された.

Two types of alkyl radicals were found to be trapped in irradiated crystals grown from polyethylene solution. One of them corresponds to the broad sextet pattern of the e.s.r. spectrum and the other corresponds to the sharp sextet pattern. The free radicals attributed to the broad sextet began to disappear at a lower temperature than the temperature at which the free radicals attributed to the sharp sextet disappeared. When butadiene molecules were brought into contact with the specimen, the decay of the free radicals corresponding to the broad sextet was accelerated. When the specimen was subjected to fuming nitric acid treatment, no broad sextet was observed. The mat of the crystals, was aligned so that the c-axes of its crystallites were perpendicular to its surface. The broad sextet showed no anisotropy when the angle between the direction of applied magnetic field and that of the c-axis of the crystallite was varied. On the other hand, the sharp component of the spectrum showed apparent anisotropy. Consequently, it can be concluded that the broad component comes from the free radicals trapped in the lamellar surface and the sharp component is attributed to the free radicals trapped in the inner part of the crystallite. Hence, the locations of these two types of free radicals have been clarified with much more certainty than before.