Effect of a new immunosuppressive agent, KF20444, in rat cardiac transplantation.
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Administration, Oral↗
Biomedical subjects
A Kishida
Publications and source records attributed to A Kishida.
Dose-dependent study of a novel immunosuppressant, FTY720, with the canine renal allograft transplantation model.
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Analysis of Variance↗
Evaluation of biological responses to polymeric biomaterials by RT-PCR analysis III: study of HSP 70, 90 and 47 mRNA expression.
In this study, in order to analyze how cells recognize biomaterials, mRNA was evaluated on various substrates as shown in the attached HeLa S3 cells. The expressed Heat-Shock Protein (HSP) 70A, 70B, 90 and 47 mRNA were isolated and detected using the RT-PCR method. As a result, 70B, 90 and 47 mRNA expressions varied with differences in the hydrophilicity hydrophobicity of the substrates. HSP mRNAs outcome was induced significantly in the HeLa S3 cells that had adhered onto the hydrophilic surfaces. On the other hand, in the cells that had adhered to the hydrophobic surfaces, HSP mRNAs expressions were low. In the non-adhered HeLa S3 cells the tendency found in HSP 70B and HSP 47 mRNA's expressions was the same as that found in adhered cells, while there were no significant differences in the HSP 90 mRNA expression among either of the samples. We have concluded that HSP mRNAs expression is an important marker in the study of cell-polymer interactions.
Biocompatible Materials↗
Synthesis and anticoagulant activity of sulfated glucoside-bearing polymer.
Poly(glucosyloxyethyl methacrylate) sulfate [poly(GEMA) sulfate], which contains sulfated glucoside residues, was prepared by the reaction with N,N-dimethylformamide (DMF)/sulfur trioxide (SO3) complex. The degree of sulfation was easily controlled by changing the amount of DMF/SO3 complex added and reaction time. The total human blood clotting time in the presence of poly(GEMA) sulfate was prolonged by increasing the dose or the degree of sulfation of the polymer. The anticoagulant activity of poly(GEMA) sulfate was also compared with that of dextran sulfate, poly(styrenesulfonic acid), poly(vinylsulfuric acid), and heparin. The result suggests that sulfated saccharide residues are essential for endowing anticoagulant activity to synthetic polymer.
Anticoagulants↗
Efficiency and biocompatibility of a polyethylene glycol grafted cellulosic membrane during hemodialysis.
Dialytic efficiency and biocompatibility of a new modified cellulose membrane (NMC) were examined in vitro and clinically. NMC was obtained by grafting polyethylene-glycol (PEG) chains to the membrane surface of ordinary cellulose (OC), and it was expected that the random movement of PEG chains would prevent blood cells and large plasma proteins from coming into contact with the membrane surface, resulting in improving the biocompatibility and thrombogenicity of the membrane. Surface characteristics of NMC were rendered anionic and hydrophilic, however, the activations of complement and platelet systems were clearly suppressed in NMC. Minimum heparin requirement for hemodialysis was significantly lower with NMC than with OC dialyzer. No significant difference in solute and water removal was observed between the two dialyzers. These results indicate that NMC can provide increased biocompatibility and antithrombogenic effect while retaining the essential dialysis efficiency of OC.
Biocompatible Materials↗
A new type of low blood flow ECCO2R using a hemodialysis system in apneic states.
To perform low blood flow extracorporeal CO2 removal (ECCO2R), the authors developed a device for extracorporeal circulation (ECC) equipped with a dialyzer for the elimination of CO2 as bicarbonate. The major problem with this method was the decrease in blood pH. To control blood pH and clarify the limit of CO2 elimination using this method, a study with apneic dogs was performed. Six anesthetized mongrel dogs were intubated and paralyzed with a muscle relaxant. Vascular access was achieved with a venovenous bypass. ECC was initiated under apneic oxygenation (100% O2, 10 cm H2O continuous airway pressure), and the CO2 concentration in the airway outlet was measured. The CO2 was converted to bicarbonate using systemic infusion of trihydroxy-methylamino methane (THAM), and the generated bicarbonate was removed by hemodialysis. Blood flow rate in the ECC was 15 ml/kg/min, and the duration of ECC was 5 hr. During ECC, the hemodynamic parameters of the dogs were stable, and the PaCO2 remained at about 90 mmHg with a PaO2 above 350 mmHg; CO2 elimination from the airway was negligible.
Acid-Base Equilibrium↗
A bioartificial ventricle used as a totally implantable circulatory assist device.
The authors designed a totally implantable circulatory assist device consisting of a bioartificial ventricle composed of a skeletal muscle ventricle lined with a bioartificial endocardium. The bioartificial endocardium consists of a structural matrix made of a polyurethane porous membrane, fragmented blood vessels, and collagen gel. The authors prepared the polyurethane porous membrane by solvent cocasting with salt powder. They used collagen gel with fragmented goat carotid vein to perform in vitro construction of the bioartificial endocardium. For in vivo construction of the bioartificial endocardium, the authors used a modified version of the tissue fragment method for vascular prostheses. The authors prepared suspensions of tissue fragments using collagen gel with fragmented goat carotid artery. They used a highly porous fabric vascular prosthesis as a structural matrix; tissue fragments were entrapped on the outer surface of the prosthesis, and the prosthesis then was implanted into the carotid artery of four adult goats. In specimens 1 and 3 months postimplantation, cells from the fragmented tissue regenerated an endothelium-like monolayer sheet on the inner surface of the prostheses. Output of a prototype bioartificial ventricle reached 660 ml/min at an afterload of 60 mmHg and a preload of 20 mmHg. Based on these data, the authors conclude that the bioartificial ventricle is promising as an implantable device with excellent antithrombogenicity.
Animals↗
Novel instrumentation monitoring in situ platelet adhesivity with a quartz crystal microbalance.
The quartz crystal microbalance (QCM) in a solution is capable of sensing an extremely small mass change in the nanogram range. In this article, the authors attempted to apply QCM to in situ continuous monitoring of platelet adhesion in plasma. The instrumentation consisted of a piezoelectric quartz crystal vacuum-deposited with gold and connected to two electrodes, an oscillation circuit, a frequency counter, and a DC source (5 V), coupled with a personal computer, a television monitor, and a printer. The authors noted resonant frequency shifts to determine weight increase upon cell adhesion. A QCM sensor, with the sensitivity of 1 ng/Hz, was placed horizontally in platelet poor plasma. The authors did not observe any measurable frequency shift upon adding a suspension of non-adherent cells, such as red blood cells and prostaglandin I2-sensitized platelets, indicating that QCM does not count the increase in the mass of cells that simply settled on the quartz. They did observe, however, a time-dependent frequency shift upon addition of platelet rich plasma. Coupled with visual determination of numbers of adherent platelets and their morphology under scanning electron microscopy, they found that the magnitude of shift and its time dependence seem to correlate not only numbers of adherent platelets, but to their spreading state, indicating that QCM detects only the weight at the focal contact region of adherent cells. This suggested that the former contributes to the early phase of the frequency shift, and the latter contributes to a shift change after a longer period of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Preparation of an RGD ALB conjugate. In vitro analysis of cellular responses.
RGD (Arg-Gly-Asp) tripeptide was identified as the minimal active core peptide sequence common to adhesive proteins. In this paper, the authors report preparation of RGD containing peptide albumin conjugate (RGD ALB), and its effects on cellular adhesive function in vitro. RGD ALB was prepared via a coupling reaction of albumin with pentapeptide (GRGDS; Gly-RGD-Ser) by water soluble carbodiimide. Bovine endothelial cells (ECs) adhered to and spread well on a surface coated with RGD ALB, whereas few ECs adhered on surfaces coated with GRGESP-albumin conjugate (GRGESP peptide with little cell attachment activity; false control) and albumin. Cellular behavior, such as adhesion, spreading, growth, and migration, on surfaces coated with GRD-ALB, fibronectin (FN), and vitronectin (VN) were quantitatively examined. Adherent cell number on RGD ALB coated surfaces was larger than on those coated with FN and VN. Cell morphology on RGD ALB coated surfaces was similar to that on FN coated surfaces. The cell growth and migration activities on RGD ALB coated surfaces were almost equal to those coated with FN and VN. Thus, RGD ALB was found to promote cell adhesion, migration, and growth as effectively as fibronectin. This indicates that an artificial adhesive protein, simply derived with bioactive peptidyl ligand, can find versatile applications in fields in which cellular events play a critical role--for example, extracellular matrices and wound healing promotion aids.
Albumins↗
Experimental study of bioactive polyurethane sponge as an artificial trachea.
An artificial trachea that has tissue reconstructive activity and elasticity that matches a biologic trachea was fabricated using a polyurethane sponge (PS). The inner surfaces of the PS were modified by immobilizing collagen, fibronectin, RGD peptide, a coating of collagen, and apatite. Two PS pore sizes were prepared, 150 to 350 microns (small pore) and 350 to 710 microns (large pore). When they were implanted in the subcutaneous tissue of rats, study of the implantation showed severe inflammatory cell infiltration with the treated PS, especially with collagen and collagen coating. Infiltration and maturity of fibroblasts inside the PS were noted with fibronectin. Infiltration of inflammatory cells and fibroblasts was noted with small pore PS compared with large pore PS. Partial tracheal defects were patched with PS. Better epithelization of PS patches was observed with fibronectin and apatite compared with the others. The artificial trachea made of PS was transplanted into the tracheas of dogs. No separation of the anastomosis and tissue reconstruction of the artificial trachea wall were observed; however, sputum absorption and tracheal granulation were seen.
Amino Acid Sequence↗
Immobilization of human thrombomodulin onto biomaterials. Comparison of immobilization methods and evaluation of antithrombogenicity.
Human thrombomodulin (hTM), which is a newly described endothelial cell associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant, was immobilized on to various substrates by two immobilization methods. As the substrates of immobilization, poly(acrylic acid) surface grafted poly(ethylene) (PAAc-g-PE) film, poly(vinylamine) surface grafted poly(ethylene) film, and PAAc surface grafted nylon were used. For immobilization, simultaneous preactivation methods were used. The effect of the immobilization reaction on hTM activities, the comparison of the activities of immobilized hTM with those of free hTM, and the effect of the thrombin incorporation on antithrombogenic activity were studied. The hTM immobilized onto PAAc-g-PE by preactivation showed the highest antithrombogenic activity. The thrombin incorporation affected protein C activation activity but not the fibrinogen clotting time. hTM immobilized nylon showed greater antithrombogenicity in vitro.
Anticoagulants↗
In vivo and ex vivo evaluation of the antithrombogenicity of human thrombomodulin immobilized biomaterials.
Human thrombomodulin (hTM) is a newly described endothelial cell associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Focusing on the establishment of the practical evaluation of hTM immobilized materials, the activity of immobilized hTM was evaluated by in vivo and ex vivo blood contacting tests. As the basis for immobilization, regenerated cellulose films and hollow fibers were used. For the in vivo test, hTM immobilized cellular hollow fibers were implanted into dog blood vessels. Using hTM immobilized cellulose hollow fibers, a small scale dialyzer was assembled and its antithrombogenic activity was studied using human blood. As a result, it was revealed that the immobilized hTM still has co-enzymatic activity for activation of Protein C and anticoagulant activity. The coagulation time of the human blood passed through the hTM immobilized small dialyzer was effectively prolonged. It is expected that hTM immobilized cellulose should be a useful antithrombogenic biomaterial.
Animals↗
Clinical effects of a polyethylene glycol grafted cellulose membrane on thrombogenicity and biocompatibility during hemodialysis.
The biocompatibility and thrombogenicity of polyethylene-glycol (PEG)-grafted cellulose hemodialysis (HD) membranes (PEGC) were investigated in cross-over HD of five HD patients with ordinary cellulose (OC). The PEGC significantly suppressed transient leukocyte and thrombocytopenia, and release of C3a, beta-thromboglobulin and platelet factor 4, in corresponding with the quantity of grafted PEG. HD with PEGC resulted in lower granulocyte elastase production, protein and blood cells adsorption on the membrane surface than those with OC. Minimum heparin in HD with PEGC was three times lower than that with OC, with the thrombin-antithrombin III complex elevation lower than that in HD with OC. The results indicate that the grafted PEG effectively suppresses blood and membrane interaction, thus improving biocompatibility and reducing thrombogenicity in clinical HD.
Biocompatible Materials↗