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Biomedical subjects

Junji Watanabe

Publications and source records attributed to Junji Watanabe.

At least 37 records · Page 2Linked to original sources

Electric-field-induced transition between the polarization-modulated and ferroelectric smectic- C(S) P(F)* liquid crystalline states studied using microbeam x-ray diffraction.

We report x-ray microbeam studies of a bent-core liquid crystalline material with chiral citronellyl tails. This material has an equilibrium polarization-modulated smectic- CP (PM-SmCP) state exhibiting the B7 texture upon slow cooing from the isotropic while a metastable chiral synclinic ferroelectric Sm-CP state (Sm- C(S) P(*)(F) ) is obtained on quenching from the isotropic. The polarization modulated phase PM-Sm C(S) P(*)(F) shows typical x-ray patterns having multiple satellite peaks around the first-order layer reflection, indicating undulated layers, while the metastable Sm- C(S) P(*)(F) state exhibits a single layering peak indicating flat layers. The Sm- C(S) P(*)(F) state is also induced by the application of an electric field larger than the threshold field ( E(th) ) and thermally returns to the polarization modulated PM-Sm C(S) P(*)(F) structure.

Journal Article↗

Design of functional hollow fiber membranes modified with phospholipid polymers for application in total hemopurification system.

In this study, we prepared cellulose acetate (CA) hollow fiber membranes (HFMs) modified with poly (2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate)(PMB30 and PMB80) by the dry-jet wet spinning process. The physical and chemical structures of the HFMs were controlled in order to design highly functional HFMs that had suitable performance to each targeting HFM device used in a total hemopurification system. The CA HFMs modified with the MPC polymer, such as CA/PMB30, CA/PMB80, and CA/PMB30-80 HFMs, were successfully prepared by controlling the spinning conditions. The modified HFMs showed an improved performance in solute and water permeability, due to the modification by the hydrophilic MPC polymers. The CA/PMB30 and CA/PMB80 showed a high potential in an application for a high performance hemocompatible plasmapheresis and hemofilter device. Furthermore, CA/PMB30-80 HFM, modified asymmetrically with PMB30 and PMB80, showed a potential for application in an advanced total hemopurification system as a highly functional scaffold for a biohybrid renal tubule, or a liver assist bioreactor device, because of their enhanced permeability, hemocompatibility, and cytocompatibility.

Animals↗

Spontaneously forming hydrogel from water-soluble random- and block-type phospholipid polymers.

The mixed aqueous solutions of two water-soluble phospholipid polymers, such as poly[2-methacryloyloxyethyl phosphorylcholine(MPC)-co-methacrylic acid(MA)] (rPMA) and poly[MPC-co-n-butyl methacrylate(BMA)] (PMB), spontaneously form a hydrogel at room temperature without any chemical treatment due to hydrogen bonding formation between the carboxyl groups. With the objective of enhancing the hydrogen bonding efficiency, we have focused on the density of the carboxyl groups by controlling the chemical structure and monomer unit sequence. Thus, a random and an ABA-block-type MPC copolymer having carboxylic acids, poly[MPC-co-4-(2-methacryloyloxyethyl) trimellitic acid(MET)] (rPMT) and poly(MA)-poly(MPC)-poly(MA) (bPMA), have been designed. The purpose of this study is to investigate the gelation mechanism and physical properties of a hydrogel composed of rPMA and PMB (ABgel), one of bPMA and PMB (bABgel), and one of rPMT and poly(MPC-co-benzyl methacrylate) (PMBz) (TZgel). The Raman spectroscopic analysis and the rheological study of the dissolution behaviors indicated that the TZgel formation occurred due to inter- and intra-molecular hydrogen bonding formation between the carboxyl groups in the rPMT. The gelation mechanism of the bABgel was investigated by the dynamic light scattering measurement, the scanning electron microscopy observation and the rheological study. The results showed that the bPMA chains aggregate in the aqueous medium and transform into a hydrogel network structure. The bPMA needed much more gelation time than the rPMA due to this transformation. There was no difference between the gelation periods of the ABgel and the TZgel. The compression strengths of the ABgel and the bABgel showed no significant difference, while that of TZgel was lower than ABgel. The reason for this is that the polymer chains and bulky side chains of rPMT inhibit rearranging into a planar conformation and forming hydrogen bondings. These results lead to the conclusion that the properties of these MPC polymer hydrogels can be controlled by not only the chemical structure of the polymer but also the monomer unit sequence containing carboxyl groups.

Biocompatible Materials↗

Perisaccadic perception of continuous flickers.

To realize perceptual space constancy, the visual system compensates for the retinal displacement caused by eye movements. It has been reported that the compensation process does not function perfectly around the time of a saccade--a perisaccadic flash is systematically mislocalized. However, observations made with transient flash stimuli do not necessarily indicate a general perisaccadic failure of space constancy. To investigate how the visual system realizes perisaccadic space constancy for continuous stimuli, we examined the time course of localization for a perisaccadic 500 Hz flicker with systematic variation of the onset timing, the offset timing and the duration. If each flash in the flicker is localized individually in the same way as a single flash, the apparent position and length of the flicker should be predicted from the time course of mislocalization of a perisaccadic flash. However, the results did not support this prediction in many respects. A dot array (of half the length of the retinal image) was perceived when the flicker was presented during a saccade, while only a single dot was perceived when the flicker was presented only before or after the saccade. A flash in a flicker was localized at a different position, depending on the onset timing, the offset timing and the duration of the flicker, even if the flash was presented at the same timing to the saccade. In general, our results support a two-stage localization in which the local geometrical configuration is first generated primarily based on the retinal information, and then localized as a whole in the egocentric or exocentric space. The localization is based on the eye position signal sampled at a time temporally distant from the saccade, which enables precise localization and space constancy for continuous stimuli.

Adult↗

Dynamic motion of phosphorylcholine groups at the surface of poly(2-methacryloyloxyethyl phosphorylcholine-random-2,2,2-trifluoroethyl methacrylate).

A series of novel random copolymers composed of hydrophilic and hydrophobic monomer units have been synthesized by a conventional radical polymerization method. As the hydrophilic monomer unit, 2-methacryloyloxyethyl phosphorylcholine (MPC) was selected because the MPC polymers are well known for their excellent bio- and blood compatibilities. The semifluorinated monomer, 2,2,2-trifluoroethyl methacrylate (TFEMA), was used as the hydrophobic monomer. The surface analysis of the copolymer by X-ray photoelectron spectroscopy, dynamic contact angle measurement, and zeta-potential measurement showed that the TFEMA unit was concentrated at the outermost surface in the dry state. The dynamic reorientation of the MPC unit occurred in the wet state because the MPC unit had a strong hydrophilic character. As a result, the monomer unit composition on the surface became almost the same as that in the bulk. Nevertheless, the properties of the surface were hydrophilic in spite of the MPC unit composition of the bulk. In particular, the amount of protein adsorbed on the surface was dramatically reduced when the MPC unit mole fraction was 0.2.

Journal Article↗

Modeling of swelling and drug release behavior of spontaneously forming hydrogels composed of phospholipid polymers.

Physically cross-linked hydrogel had been investigated in order to make use of oral polypeptide drug delivery carrier. By using 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer, we had prepared a spontaneously forming hydrogel showing controllable dissociation via pH changes. In this study, the dissociation and release of polypeptide drugs from the MPC polymer hydrogel loaded with polypeptide drugs, which had been prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB) had been executed. The polymer concentration was 10 wt.% and PMA/PMB feed ratio (A/B feed ratio) was 5/5. Insulin labeled with fluorescein-4-isothiocyanate (FITC) and cytochrome c had been loaded for the examination of the release behavior. The hydrogel in pH 1.8 aqueous solution would be swelling, for the hydrogel would absorb outside water. However, during this process, the polymer is dissoluting out from the hydrogel due to the widening of the polymer network. The cytochrome c followed anomalous transport while insulin depended on the swelling and dissolution of the polymer chains. The hydrogel showed surface erosion in neutral condition, although the hydrogel is composed of two different polymer possessing divergent physical properties. The release followed anomalous transport, but the erosion rate slightly changed with as the hydrophobicity of the loaded drugs. The total amount of the drugs released in neutral condition was larger compared to the acidic condition. When the eroded percentage and the release percentage were compared with each other, it showed that release was slightly slower than erosion, indicating that the erosion was controlling the release phenomenon.

Cytochromes c↗

Evaluation of 2-methacryloyloxyethyl phosphorylcholine polymeric nanoparticle for immunoassay of C-reactive protein detection.

To prepare novel 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymeric nanoparticle (MPC-PNP), water-soluble amphiphilic phospholipid polymer, poly [MPC-co-n-butyl methacrylate (BMA)-co-p-nitrophenyloxycarbonyl poly(ethylene glycol) methacrylate (MEONP) (PMBN)], which has active ester groups for bioconjugation on the side chains, was synthesized. MPC-PNP was prepared by a solvent evaporation technique where the poly(l-lactic acid) was used as core and PMBN was applied as an emulsifier and a surface modifier under systematical design of well-arranged phospholipids polar groups in its surface. Characteristics for MPC-PNP were thoroughly investigated with dynamic light scattering, electrophoresis light scattering, X-ray photoelectron spectroscopy, and field emission scanning electron microscopy measurements. Through a protein adsorption test, the phosphorylcholine group on the surface of MPC-PNPs, which had their active ester groups substituted by glycine, were shown to suppress the nonspecific adsorption of bovine serum albumin. These particles were used for C-reactive protein (CRP) detection, where anti-CRP monoclonal antibodies were immobilized on the MPC-PNP using the active ester group, while the remaining active ester groups were thoroughly reacted with glycine. The detection limit about serum-free CRP in the calibration curve was shown to extend from 0.01 to 10 mg/dL when anti-CRP antibody immobilized MPC-PNP was used for serum-free CRP detection. This compares favorably with measurement using polystyrene nanoparticles that were shown to detect from 0.1 to 10 mg/dL by an immunoagglutination technique. Also, for the detection of CRP in serum, MPC-PNP was shown to give the same calibration curve explained by the efficient suppression of nonspecific binding. Furthermore, denaturation of immobilizing anti-CRP antibody on the MPC-PNP hardly occurred despite increasing the temperature. It is concluded that MPC-PNP is unique due to the design of its interfacial properties, also it will perform well in a diagnostic immunoassay because of its optimized material properties.

Adsorption↗

The characteristics of spontaneously forming physically cross-linked hydrogels composed of two water-soluble phospholipid polymers for oral drug delivery carrier I: hydrogel dissolution and insulin release under neutral pH condition.

Hydrogels bearing a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine (MPC), were prepared from two aqueous solutions of polymers, water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB). The hydrogel, which was formed by physical cross-linking spontaneously without any chemical reactions and/or any physical stimuli, showed a controllable insulin release through a pH change in the medium by changing the hydrogen bonds. In this study, the mechanical strength, erosion of the hydrogel caused by polymer dissociation, and the release of insulin were examined with attention to the following three parameters of the MPC polymer: molecular weight of the polymers, composition of PMA and PMB (PMA/PMB ratio), and polymer concentration inside the hydrogel. The hydrogel with the highest mechanical strength was obtained at a PMA/PMB ratio = 3/7 (v/v, by volume ratio) while the hydrogel with the slowest dissolution was obtained at a ratio of 5/5 (v/v). The release was in good match with the dissolution and followed anomalous transport for all, but the diffusion exponent n changed according to the PMA/PMB ratio. An increase in the polymer concentration inside the hydrogel caused an increase in the mechanical strength of the hydrogel. When the polymer concentration was more than 20 wt.%, the absorption of water under neutral pH condition (pH 6.8) was observed. The release of insulin was suppressed below 10% during the swelling process of the hydrogel under neutral pH condition, while release was accelerated during the erosion process of the hydrogel. The relationship between erosion of the hydrogel and the release of the insulin depended on the erosion process of the hydrogel but differed according to the PMA/PMB ratio.

Administration, Oral↗

Beneficial effect of rotational atherectomy with low platform speed on late outcomes.

BACKGROUND: Modification of rotational atherectomy (RA) procedures might be expected to alter restenosis rates. METHODS AND RESULTS: From June 1998 (period 2), platform speed was decreased to 150,000-160,000 rpm from the 170,000-190,000 rpm performed from August 1997 to May 1998 (period 1). Patients for the two periods (period 1: 62 patients, 70 lesions; period 2: 85 patients, 91 lesions) demonstrated comparable clinical and angiographic baseline data, allowing immediate and late outcomes to be evaluated for comparison. Restenosis rates in periods 1 and 2 were 57.9% and 33.8%, respectively (P=0.01). Platform speed and lesion length were independent predictors of restenosis by multivariate logistic regression analysis. CONCLUSIONS: RA with a low platform speed (150,000-160,000 rpm) can be performed with a high success rate and with a lower incidence of restenosis than with a high platform speed (170,000-190,000 rpm).

Aged↗

Effect of water-soluble phospholipid polymers conjugated with papain on the enzymatic stability.

To maintain enzymatic activity during long-term storage by conjugation with water-soluble 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers (PMPC-COOH) having various molecular weights with a carboxylic group on the terminal, such compounds were synthesized as a polymer modifier using a photoinduced living radical polymerization technique. A poly(ethylene oxide) with a carboxyl group (PEO-COOH) was used as the control. The PMPC-COOHs were reacted with the amino groups of the enzyme, papain, via amide bonds. With an increase in the molecular weight in the range between 5 and 20K of the PMPC-COOH, the modification degree and alpha-helix content of the conjugated papain slightly decreased, but the remaining enzymatic activity did not depend on the molecular weight of the PMPC-COOH. However, when a much higher molecular weight PMPC-COOH (40K) was conjugated with a reduction in the modification degree, alpha-helix content was higher compared with the other PMPC-conjugated papain. Modification with PEO-COOH showed little reduction of the alpha-helix content of papain. The time dependence of the remaining enzymatic activity of the polymer-conjugated papains was evaluated during storage at 40 degrees C. The native papain diminished activity within one week. PEO-conjugated papain had decreased activity with time, but after one week it had half its initial level. The same tendency was observed when papain was modified with PMPC-COOHs 5 and 40K, that is, the enzymatic activity did not decrease even when they were stored for 4 weeks. We concluded that the PMPC chain could stabilize the enzyme by control of the molecular weight of the PMPC and modification degree to the enzyme.

Biocompatible Materials↗

Polyethylene/phospholipid polymer alloy as an alternative to poly(vinylchloride)-based materials.

To develop new biomaterials for making medical devices, polymer alloys composed of a phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and polyethylene (PE) were prepared. The PE/PMPC alloy membrane could be obtained by a combination of solution mixing and solvent evaporation methods using xylene and n-butanol mixture as a solvent. Moreover, thermal treatment was applied to improve the mechanical properties of the PE/PMPC alloy membrane. In the PE/PMPC alloy membrane, the PMPC domains were located not only inside the membrane but also at the surface. Surface analysis of the PE/PMPC alloy membrane with X-ray photoelectron spectroscopy, wettability evaluation, and dynamic contact angle measurements revealed that the phospholipid polar groups in the PMPC covered the surface even after thermal treatment. Blood compatibility tests with attention to platelet adhesion and change in morphology of adhered platelets showed that the PE/PMPC alloy membrane had excellent platelet adhesion resistance. We finally concluded that the PE/PMPC alloy could be used as biomaterials instead of poly(vinyl chloride)-based materials.

Alloys↗

Cellulose acetate hollow fiber membranes blended with phospholipid polymer and their performance for hemopurification.

Commercially available hollow fiber membranes (HFMs) made from synthetic polymers, including cellulose acetate (CA) HFMs, used as hemopurification membranes, need to improve in hemocompatibility, by suppressing protein adsorption and clot formation. In this study, CA HFMs blended with 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer (PMB30 composed of MPC and n-butyl methacrylate (BMA)) were prepared by a dry-jet wet spinning process. Their performances were evaluated by characterizing their properties such as structure, permeability and protein adsorption. CA/PMB30-blend HFMs showed structure changes such as increase of porosity, development of large pores and decreasing of the thickness of the active layer. And the structure and permeability of CA/PMB30-blend HFMs were controllable by changing preparation conditions. Also, the CA/PMB30-blend HFMs had good permeability, low protein adsorption and low fouling property during the permeability experiment in comparison with CA HFMs, because the hydrophilic and hemocompatible MPC copolymer (PMB30) existed on the surface of the HFM.

Adsorption↗

Surface characteristics of block-type copolymer composed of semi-fluorinated and phospholipid segments synthesized by living radical polymerization.

A series of random and block copolymers composed of hydrophilic and hydrophobic monomer units have been synthesized by the free and living radical polymerization methods, respectively. The hydrophilic monomer unit, 2-methacryloyloxyethyl phosphorylcholine (MPC), was selected because the MPC polymers are well-known for their excellent bio- and blood compatibilities. The semi-fluorinated monomer, 2,2,2-trifluoroethyl methacrylate (TFEMA), was used as the hydrophobic monomer unit. Several analyses of the copolymer surface showed that the TFEMA unit was concentrated at the outermost surface on the random copolymer surface and characteristics of MPC unit was dominant on the block copolymer with a low-MPC-unit composition in the dry state. A reorientation of the MPC unit occurred dynamically in the wet state because of the strong hydrophilicity of the MPC units. In the case of the block copolymer with a low-MPC-unit composition, the surface was covered with the MPC units in the wet state. As a result, the amount of the adsorbed bovine plasma fibrinogen and bovine serum gamma-globulin on the block copolymer surface was reduced dramatically.

Adsorption↗

Hydrogen-bonding-driven spontaneous gelation of water-soluble phospholipid polymers in aqueous medium.

It has been found that mixing of two kinds of water-soluble phospholipids polymers, such as poly(2-methacryloyloxyethyl phosphorylcholine-co-methacrylic acid) (PMA) and poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB), spontaneously forms a hydrogel in aqueous medium at room temperature without any chemical treatment. However, the mechanism of spontaneous gelation has not been clarified yet. The purpose of this study is to investigate the gelation mechanism of the hydrogel. Moreover, effects of ions on gelation and dissolution behavior were observed. We investigated the mechanism of the hydrogel formation by spectroscopic techniques and a rheological method with attention to the interactions between polymer chains. Both Raman spectroscopic analysis and FT-IR analysis revealed that carboxyl groups in methacrylic acid (MA) formed dimer when two polymer solutions were mixed, and the results of the rheological study showed dissociation of carboxyl groups caused dissolution of the hydrogel. Thus, the gelation occurred due to the formation of dimers by hydrogen bonding which acts as a physical cross-linking of polymer chains. The hydrogel dissolved in a large amount of aqueous medium. We also observed the addition of inorganic salts during the preparation of the hydrogel affected the gelation and dissolution behaviors by a rheological and a weight measuring method, respectively. The gelation period became longer in the presence of NaCl and CaCl2 compared with that in the absence of these salts. NaCl and CaCl2 disturbed the formation of hydrogen bonding between carboxyl groups by stabilization of carboxylate anion of the MA units. On the other hand, addition of FeCl3 made the gelation period shorter and stabilized the hydrogel in the aqueous medium. This is because FeCl3 can suppress dissociation of the carboxyl groups by acidic condition of FeCl3 aqueous solution and cross-link the carboxylate anions in the PMA effectively.

Calcium Chloride↗

Blue phases induced by doping chiral nematic liquid crystals with nonchiral molecules.

The emergence of the blue phases I and II that are thought to exist in highly chiral systems has been found in chiral nematic liquid crystals (N* LCs) when they are doped with achiral bent-core liquid crystals (banana mesogens). The same effect was also observed by adding racemic 4-(1-methylheptyl oxycarbonyl)phenyl 4'-octyloxybiphenyl-4-carboxylate (MHPOBC), while achiral terephthal-bis(p-butylaniline) (TBBA) was not effective. The difference was attributed to the different conformations, i.e., MHPOBC is known to have a bent shape, but not TBBA. The doping effect is more remarkable in N* LCs with higher chiral content for both banana mesogens and MHPOBC. This unusual doping effect was attributed to selective chiral interaction between the chiral conformers of guest molecules and chiral host molecules and/or the decrease of the surface elastic constant on adding bent-shaped guest molecules.

Journal Article↗

Endotoxin contamination of ovalbumin suppresses murine immunologic responses and development of airway hyper-reactivity.

The reversible airway hyper-reactivity (AHR) of asthma is modeled by sensitizing and challenging mice with aerosolized ovalbumin. However, the C57BL/6 murine strain does not display the large increase in circulating IgG and IgE antibodies found in human atopy and asthma. We found that commercial ovalbumin was contaminated with lipopolysaccharide (LPS) in amounts sufficient to fully activate endothelial cells in an in vitro assay of the first step of inflammation. Desensitization of TLR4 by LPS pretreatment suppressed the inflammatory effect of ovalbumin. The presence of LPS was occult, because it does not require serum presentation and, like the LPS of Salmonella minnesota, was not suppressed by polymyxin B. Purified ovalbumin did not activate endothelial cells in vitro; however, endotoxin-free ovalbumin was far more effective than commercial material in stimulating IgE production and respiratory dysfunction in a C57BL/6 murine model of AHR. Moreover, endotoxin-free ovalbumin induced lung inflammation with alveolar enlargement and destruction in a histologic pattern that differed from the changes caused by commercial, endotoxin-contaminated ovalbumin. Reconstitution of purified ovalbumin with S. minnesota LPS decreased lung inflammation, decreased changes in lung function, and suppressed anti-ovalbumin antibody production. We conclude endotoxin contaminates ovalbumin preparations and that endotoxin co-administration with the ovalbumin antigen creates a state of tolerance in a murine model of AHR. Co-exposure to endotoxin and antigen occurs in humans through organic dusts, so murine models of AHR may reflect the clinical situation, but models based on commercial ovalbumin do not accurately reflect the effect of protein antigen alone on animal physiology.

Airway Obstruction↗

Local layer structures in circular domains of an achiral bent-core mesogen observed by x-ray microbeam diffraction.

The local layer structures have been investigated by x-ray microbeam diffraction in the circular domains of the SmCP phase of a banana-shaped molecule. Originally, the molecules form tilted layers with a certain tilt angle as well as nontilted ones. The application of a low electric field induces a tilted layer with a continuous change of the tilt angle; i.e., the tilted layer gradually changes the tilt angle, finally being upright at the center of circular domains. Upon application of a high electric field, the smectic layer forms a cylindrical-type structure. The layer structure changes from cylindrical to onionlike after turning off the high field.

Journal Article↗