Biomedical subjects
Publications and source records attributed to T Motomura.
We performed endoscopic carpal tunnel release in four hands in three patients suffering from radial dysplasia due to thalidomide embryopathy. Carpal canal pressure measurements results confirmed the diagnoses. All operations were successfully performed and resulted in no complications. Tingling sensation and sensory disturbances of the hands subsided.
OBJECTIVE: The Baylor Gyro BVAD is under development with the final goal of establishing a totally implantable biventricular assist system (BVAD). The aim of this study was to evaluate the safety, reliability, and effectiveness of the device in a long-term in vivo model. METHODS: The BVAD was implanted into eight calves for longer than 4 weeks in a biventricular bypass fashion, with the native heart remaining. Pump performance was assessed with the system's digital data acquisition unit. Postoperatively, anticoagulation was maintained with i.v. heparin perfusion (ACT< or = 250 sec) gradually replaced by coumadin. Treadmill exercise tests were performed daily following a 10-day reconvalescence period after surgery. RESULTS: The animals were kept alive for 37-90 days. The pumps yielded average flows of 5.3 +/- 1.1 l/min and 4.9 +/- 0.7 l/min for the LVAD and RVAD, respectively. Power consumption was 8.2 +/- 2.7 W and 9.6 +/- 4.7 W at 1935 +/- 123 rpm and 2015 +/- 365 rpm, respectively. All cases exhibited low hemolysis; renal and liver function were kept normal throughout the experiments. The animals demonstrated no thromboembolic neurological symptoms and tolerated moderate treadmill exercise. CONCLUSION: The Baylor Gyro BVAD demonstrated effective and reliable in vivo performance with acceptable biocompatibility. Based on these studies, we conclude that the system will be suitable as a long-term totally implantable BVAD for uses intended for longer than two years.
In this study, the association of the Pro12Ala peroxisome proliferator-activated receptor gamma2 (PPARgamma2) polymorphism with atherosclerosis was examined in a Japanese Type 2 diabetic population. PPARgamma has been identified as a key regulator of adipogenesis. Recently, some studies reported that the Pro12Ala polymorphism was associated with resistance to Type 2 diabetes. It is well-known that Type 2 diabetes is closely related with disorder of lipid metabolism as well as impaired glucose homeostasis, resulting in atherosclerosis. We aimed to evaluate the association between carriers of the Pro12Ala PPARgamma2 mutation and clinical profiles concerning atherosclerosis besides plasma glucose and lipid concentrations. Screening for the mutation was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method among 154 Type 2 diabetic patients. The homozygotes of the Pro12 allele were 143 (93%), the heterozygotes of the Pro12 and Ala12 allele were 11 (7%) and the homozygote of the Ala12 allele was not detected. The group with the Ala12 allele had a significantly lower value of carotid artery intima-media thickness (IMT) than that without it, although there was no difference between two groups in sex, age or other clinical variables we examined. The Pro12Ala PPARgamma2 polymorphism may be associated with carotid artery IMT values in Type 2 diabetes mellitus.
The ultrastructure of mitosis and cytokinesis in Scytosiphon lomentaria (Lyngbye) Link zygotes was studied by freeze fixation and substitution. During mitosis, the nuclear envelope remained mostly intact. Spindle microtubules (MTs) from the centrosome passed through the gaps of the nuclear envelope and entered the nucleoplasm. In anaphase and telophase, two daughter chromosome masses were partially surrounded with endoplasmic reticulum. After telophase, the nuclear envelope was reconstructed and two daughter nuclei formed. Then, several large vacuoles occupied the space between the daughter nuclei. MTs from the centrosomes extended toward the mid-plane between two daughter nuclei, among the vacuoles. At that time, Golgi bodies near the centrosome actively produced many vesicles. Midway between the daughter nuclei, small globular vesicles and tubular cisternae accumulated. These vesicles derived from Golgi bodies were transported from the centrosome to the future division plane. Cytokinesis then proceeded by fusion of these vesicles, but not by a furrowing of the plasma membrane. After completion of the continuity with the plasma membrane, cell wall material was deposited between the plasma membranes. The tubular cisternae were still observed at the periphery of the newly formed septum. Microfilaments could not be observed by this procedure. We conclude that cytokinesis in the brown algae proceeds by fusion of Golgi vesicles and tubular cisternae, not by a furrowing of the plasma membrane.
We studied coronary artery bypass grafting (CABG) in patients with renal dysfunction. From April 1994 to October 1999, 59 patients with renal dysfunction underwent CABG. The patients were divided into 2 groups: group A: 18 patients with end stage renal disease who were receiving hemodialysis, group B; 41 patients with creatinine levels higher than 1.5 mg/dl who were not supported by dialysis. We compared and analyzed the findings of there 2 groups. Regarding preoperative factors, the incidence of old myocardial infarctions, diabetes mellitus and old cerebral infarctions did not differ significantly between the 2 groups. Regarding perioperative factors, the incidence of the number of vessel diseases, emergency operations, operation times and blood transfusions did not differ significantly between the 2 groups. Regarding the post-operative course, the hospital mortality rates demonstrated low levels in 2 groups. The graft patency of group A was 95%, while it was 99% in group B. The post-operative in-hospital days was 24.8 days in the group A, while it was 30.1 days in the group B. No significant difference was observed between the 2 groups. As a results, post-operative hemodialysis was needed in 8 of the patients who underwent on-pump CABG from group A. The actual survival rates were 75.3% in group A and 84.3% in group B at 4 years. The cardiac event free rate for group A was 93.3%, while it was 97.5% in group B at 4 years. In conclusion, CABG may improve the post-operative outcome in renal dysfunction patients. In addition, the use of off-pump CABG is also considered to achieve a better renal function than on-pump CABG.
We measured the fully carboxylated prothrombin levels using the Carinactivase-1 (CA-1) test and thus compared prothrombin levels between patients having atrial fibrillation (Af) without pacemaking and those having sick sinus syndrome due to Af with cardiac pacemaker implantation during anticoagulation therapy with warfarin. Total plasma samples were assayed for the CA-1 test, the prothrombin time international normalized ratio (PT-INR) and the thrombotest (TT). This prospective randomized study was carried out on 641 samples obtained at the Fukuoka University Hospital Department of Cardiovascular Surgery between May 1997 and March 1999. The patients were divided into 2 groups consisting of: group A; 144 patients having sick sinus syndrome due to Af implanted with a cardiac pacemaker who were treated with warfarin, group B; 497 patients atrial fibrillation without pacemaking who were treated with warfarin. The prothrombin levels in each group were 65.5 +/- 25.2 and 76.1 +/- 47.7 micrograms/ml, respectively. The normal prothrombin levels of group A decreased more significantly than in group B. Therefore, the PT-INR and TT were not significantly different between groups A and B. The dose of warfarin in each group was 2.4 +/- 1.0 and 2.6 +/- 1.4 g/day, respectively. The dose of warfarin in group A therefore decreased significantly different more than in group B. In conclusion, the normal prothrombin levels of patients atrial fibrillation increased more significantly than patients having sick sinus syndrome due to Af implanted with a cardiac pacemaker.
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Lotus japonicus has attracted attention as a model plant legume for molecular genetic research, and several mutants defective in nodulation and mycorrhizal symbiosis have been developed from the standard accession Gifu B-129. However, as a model system, Gifu has long lacked an appropriate crossing partner for use in various genetic analyses. In a search for an appropriate partner for Gifu, we have collected plants from 15 localities throughout Japan, and analyzed their levels of DNA polymorphism (also in comparison to the African species L. filicaulis) by AFLP (Amplified Fragment Length Polymorphism) combined with the use of a high-throughput electrophoretic screening system termed HEGS (High-efficiency genome scanning) developed by us, using 31 primer pairs. Plants of the accession Miyakojima MG-20 showed the highest level of polymorphism relative to Gifu (over 4%). When HEGS is used for screening, this level is sufficient to permit systematic positional cloning of mutant genes. Segregation in the F2 of the Gifu-derived symbiotic mutations Ljsym70, Ljsym72, Ljsym74-1 (alb1-1) and Ljsym78-1 from a cross with Miyakojima was normal, while the ratios seen from a cross with L. filicaulis were distorted. Miyakojima displays several traits that distinguish it from other Japanese accessions: low concentrations of anthocyanin in the stem and petals, few trichomes, a more upright habit, broad leaflets and petals, and large black seeds. The first two traits, which are controlled by single recessive genes, serve as useful markers for following mutant crosses.
Previously, it was demonstrated that any human immunodeficiency virus type 1 (HIV-1) strain proliferating in peripheral blood mononuclear cells (PBMCs) in vitro, and resuspended in seronegative plasma, could be captured efficiently (mean > 95%) by a porous polypropylene (PP) membrane modified cationically. We investigated if this cationic membrane could capture HIV-1 obtained from seropositive plasma, and confirmed whether this membrane was effective for the preparation of safe plasma products against HIV-1 transmission. Thirty-six seropositive plasma samples derived from HIV-1 positive cohorts in New York and Lusaka (Republic of Zambia), including 18 cases of acquired immunodeficiency syndrome (AIDS) related complex, AIDS and five terminal cases of AIDS, were filtered through the cationic membrane to determine the reduction of RNA concentration, the gag p24 concentration, and infectious titer. Only a small reduction in RNA concentration (mean < 20%) and almost no decrease in gag concentration (mean < 2%) were obtained, despite the fact that the infectivity was eliminated entirely by the filtration. Due to the possibility that anti-HIV-1 antibodies in patients' plasma combine with HIV-1, laboratory-adapted HIV-1(HTLV-IIIB) was mixed with seropositive plasma to test the effect of antibodies on HIV-1 adsorption, and also to investigate the interfacial electrokinetic potential (zeta-potential) of both intact and plasma-treated HIV-1. The zeta-potential of HIV-1(HTLV-IIIB) in the presence of seropositive plasma was neutral as opposed to negative when stored in seronegative plasma or culture medium. Also the rate of HIV-1 capture by the membrane, as determined by the reduction in RNA concentration, sank from 95% to 20%, the same capture percentage observed when filtering plasma of patients. These findings suggested that in patients' plasma, the antibody-masked HIV-1 comprise most of the viral population, and was not trapped on the cationic membrane because of its electrostatic character. Conversely, the cationic membrane was thought to adsorb antibody-free HIV-1 exclusively. It was suggested that each viral swarm had its own zeta-potential, and this difference in electrostatic character determined the extent of the viral adsorption by the cationic membrane.
An experimental silicone hollow fiber membrane oxygenator for long-term extracorporeal membrane oxygenation (ECMO) was developed in our laboratory using an ultrathin silicone hollow fiber. However, the marginal gas transfer performances and a high-pressure drop in some cases were demonstrated in the initial models. In order to improve performance the following features were incorporated in the most recent oxygenator model: increasing the fiber length and total surface area, decreasing the packing density, and modifying the flow distributor. The aim of this study was to evaluate the gas transfer performances and biocompatibility of this newly improved model with in vitro experiments. According to the established method in our laboratory, in vitro studies were performed using fresh bovine blood. Gas transfer performance tests were performed at a blood flow rate of 0.5 to 6 L/min and a V/Q ratio (V = gas flow rate, Q = blood flow rate) of 2 and 3. Hemolysis tests were performed at a blood flow rate of 1 and 5 L/min. Blood pressure drop was also measured. At a blood flow rate of 1 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 72.45 +/- 1.24 and 39.87 +/- 2.92 ml/min, respectively. At a blood flow rate of 2 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 128.83 +/- 1.09 and 47.49 +/- 5.11 ml/min. Clearly, these data were superior to those obtained with previous models. As for the pressure drop and hemolytic performance, remarkable improvements were also demonstrated. These data indicate that this newly improved oxygenator is superior to the previous model and may be clinically acceptable for long-term ECMO application.
Based on the results of in vitro studies of many experimental models, a silicone hollow fiber membrane oxygenator for pediatric cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber with a 300 microm outer diameter and a wall thickness of 50 microm. In this study, we evaluated the gas transfer performance of this oxygenator simulating pediatric CPB and ECMO conditions. Two ex vivo studies in a pediatric CPB condition for 6 h and 5 ex vivo studies in an ECMO condition for 1 week were performed with venoarterial bypass using healthy calves. At a blood flow rate of 2 L/min and V/Q = 4 (V = gas flow rate, Q = blood flow rate) (pediatric CPB condition), the O2 and CO2 gas transfer rates were maintained at 97.44 +/- 8.88 (mean +/- SD) and 43.59 +/- 15.75 ml/min/m2, respectively. At a blood flow rate of 1 L/min and V/Q = 4 (ECMO condition), the O2 and CO2 gas transfer rates were maintained at 56.15 +/- 8.49 and 42.47 +/- 9.22 ml/min/m2, respectively. These data suggest that this preclinical silicone membrane hollow fiber oxygenator may be acceptable for both pediatric CPB and long-term ECMO use.
An implantable biventricular assist device (BVAD) has been developed at Baylor College of Medicine using 2 centrifugal blood pumps. The aim of this study was to investigate the exercise-reflex response during nonpulsatile biventricular assistance and to evaluate to which degree the autoregulation of the system would accommodate the changed hemodynamic situation during physical exercise. The Baylor Gyro PI 710 BVAD has been implanted into 2 calves (strain half-Dexter) in a biventricular bypass fashion with native heart remaining. Allowing a 10 day convalescence, 2 animals were subjected to incremental exercise tests. The speed of the treadmill was increased at zero slope from 0.7 mph to 1.5 mph with increments of 0.2 mph every 3 min. During the exercise the pump flows were maintained at a fixed rate (6.93 +/- 0.01 L/min for the left ventricular assist device and 5.36 +/- 1.44 L/min for the right ventricular assist device). Hemodynamic parameters and pump performance were recorded continuously. The cardiac output (CO) and heart rate (HR) increased significantly during the exercise. CO increased from 11.1 +/- 0.3 to 13.1 +/- 0.4 L/min, and HR increased from 99 +/- 7.1 to 114 +/- 2.8 bpm, respectively. Mean aortic pressure, central venous pressure, and left arterial pressure did not change significantly. Also, no change was observed for the left and right pump flows. This totally implantable BVAD showed excellent long-term performance without any mechanical problems. It is feasible to operate without impairment under physical activity. However, the natural heart dominated the hemodynamic response during exercise under BVAD support. The left and the right pump flows did not increase spontaneously with exercise. We therefore conclude that a servo CO control system is necessary to regulate pump flows even during moderate exercise.
The Baylor Gyro permanently implantable centrifugal blood pump (Gyro PI pump) has been under development since 1995 at Baylor College of Medicine. Excellent results were achieved as a left ventricular assist device (LVAD) with survival up to 284 days. Based on these results, we are now focusing on the development of a biventricular assist device (BVAD) system, which requires 2 pumps to be implanted simultaneously in the preperitoneal space. Our hypothesis was that the Gyro PI pump would be an appropriate device for an implantable BVAD system. The Gyro PI 700 pump is fabricated from titanium alloy and has a 25 ml priming volume, pump weight of 204 g, height of 45 mm, and pump diameter of 65 mm. This pump can provide 5 L/min against 100 mm Hg at 2,000 rpm. In this study, 6 half-Dexter healthy calves have been used as the experimental model. The right pump was applied between the infundibular of the right ventricle and the main pulmonary artery. The left pump was applied between the apex of the left ventricle and the thoracic descending aorta. As for anticoagulation, heparin was administered at the first postoperative week and then converted to warfarin sodium from the second week after surgery. Both pump flow rates were controlled maintaining a pulmonary arterial flow of less than 160 ml/kg/min for the sake of avoidance of pulmonary congestion. Blood sampling was done to assess visceral organ function, and the data regarding pump performance were collected. After encountering the endpoint, which the study could not keep for any reasons, necropsy and histopathological examinations were performed. The first 2 cases were terminated within 1 week. Deterioration of the pump flow due to suction phenomenon was recognized in both cases. To avoid the suction phenomenon, a flexible conduit attached on the inlet conduit was designed and implanted. After using the flexible inflow conduit, the required power and the rotational speed were reduced. Furthermore, the suction phenomenon was not observed except for 1 case. There was no deterioration regarding visceral organ function, and pulmonary function was maintained within normal range except for 1 case. Even though the experimental animal survived up to 45 days with the flexible inflow conduit, an increase in power consumption due to thrombus formation behind the impeller became a problem. Lower rotational speed, which was probably produced by the effectiveness of the flexible inflow conduit, was speculated to be one of the reasons. And the minimum range of rotational speed was 1,950 rpm in these 6 BVAD cases and the previous 3 cases of LVAD. In conclusion, 6 cases of BVAD implantation were performed as in vivo animal studies and were observed up to 45 days. The flexible inflow conduit was applied in 4 of 6 cases, and it was effective in avoiding a suction phenomenon. The proper rotational speed of the Gyro PI 700 pump was detected from the viewpoint of antithrombogenicity, which is more than 1,950 rpm.
The capacity of chondrogenic precursor cells to migrate and proliferate in an injured area is considered to be essential for cartilage repair. We examined cell motility of chondrocytes and synovial cells in monolayer culture and the chemokinetic effects of hyaluronic acid (HA) and basic fibroblast growth factors (bFGF) on these cells. The velocity of chondrocyte migration was accelerated by giving bFGF and simultaneously administering of both HA and bFGF, but it was not affected by HA alone. The velocity of synovial cell migration was increased by HA, but not by bFGF. HA had a chemokinetic effect on synovial cells and bFGF had the same effect on chondrocytes. Treatment with exogenous HA and bFGF may be of value for repairing articular cartilage injury by recruiting chondrogenic cells and promoting migration of chondrocytes in the cartilage tissue.
Platelet adhesion and spreading is suppressed when a poly(2-methoxyethylacrylate) (PMEA) surface is used, compared with other polymer surfaces. To clarify the reason for this suppression, the relationship among the amount of the plasma protein adsorbed onto PMEA, its secondary structure and platelet adhesion was investigated. Poly(2-hydroxyethylmethacrylate) (PHEMA) and polyacrylate analogous were used as references. The amount of protein adsorbed onto PMEA was very low and similar to that absorbed onto PHEMA. Circular dichroism (CD) spectroscopy was applied to examine changes in the secondary structure of the proteins after adsorption onto the polymer surface. The conformation of the proteins adsorbed onto PHEMA changed considerably, but that of proteins adsorbed onto PMEA differed only a little from the native one. These results suggest that low platelet adhesion and spreading are closely related to the low degree of the denaturation of the protein adsorbed onto PMEA. PMEA could be developed as a promising material to produce a useful blood-contacting surface for medical devices.
Coronary artery bypass grafting (CABG) without cardiopulmonary bypass (off-pump CABG) was performed on a patient with a brain tumor. A patient with effort angina of the left anterior descending artery (LAD), and diagonal branch stenosis was referred to us for CABG. He had a mass lesion in the brain that was diagnosed as meningioma involving the internal carotid artery and a middle cerebral artery. To avoid brain complications, we performed off-pump CABG using the internal thoracic and radial arteries to the LAD and a diagonal branch. Off-pump CABG was an effective method to avoid brain complications for patients with a brain tumor involving cerebral vessels.
The influence of centrioles, derived from the sperm flagellar basal bodies, and the centrosomal material (MTOCs) on spindle formation in the brown alga Fucus distichus (oogamous) was studied by immunofluorescence microscopy using anti-centrin and anti-beta-tubulin antibodies. In contrast to a bipolar spindle, which is formed after normal fertilization, a multipolar spindle was formed in polyspermic zygote. The number of mitotic poles in polyspermic zygotes was double the number of sperm involved in fertilization. As an anti-centrin staining spot (centrioles) was located at these poles, the multipolar spindles in polyspermic zygotes were produced by the supplementary centrioles. When anucleate egg fragments were fertilized, chromosome condensation and mitosis did not occur in the sperm nucleus. Two anti-centrin staining spots could be detected, microtubules (MTs) radiated from nearby, but the mitotic spindle was never produced. When a single sperm fertilized multinucleate eggs (polygyny), abnormal spindles were also observed. In addition to two mitotic poles containing anti-centrin staining spots, extra mitotic poles without anti-centrin staining spots were also formed, and as a result multipolar spindles were formed. When karyogamy was blocked with colchicine, it became clear that the egg nucleus proceeded independently into mitosis accompanying chromosome condensation. A monoastral spindle could be frequently observed, and in rare cases a barrel-shaped spindle was formed. However, when a sperm nucleus was located near an egg nucleus, the two anti-centrin staining spots shifted to the egg nucleus from the sperm nucleus. In this case, a normal spindle was formed, the egg chromosomes arranged at the equator, and the associated MTs elongated from one pole of the egg spindle toward the sperm chromosomes which were scattered. From these results, it became clear that paternal centrioles derived from the sperm have a crucial role in spindle formation in the brown algae, such as they do during animal fertilization. However, paternal centrioles were not adequate for the functional centrosome during spindle formation. We speculated that centrosomal materials from the egg cytoplasm aggregate around the sperm centrioles and are needed for centrosomal activation.
We describe here a unique anti-HIV-1 membrane, derived from a chemically modified porous polypropylene (PP) membrane, which lowers viral infectivity upon the filtration of HIV-1 suspension. A cationic polymer, polyethyleneimine (PEI) was graft-polymerized onto the PP filter membrane (PP-PEI), and infectious HIV-1(HTLV-IIIB) derived from MOLT-4/HIV-1(HTLV-IIIB) cells (HIV-1(HTLV-IIIB(MOLT-4)) was applied. When a viral suspension of high titer (10(3.93) TCID50 ml(-1) was filtered, efficient reduction (>99%) of gag p24 antigen levels and infectious titer resulted. In a viral suspension of medium titer (10(2.37) TCID50 ml(-1), a significant decrease in the p24 antigen did not occur, although the titer was markedly reduced (>95%). Electron microscopic observation suggested that PEI induced viral aggregations under high titer conditions, and under medium titer conditions, PEI deprived HIV-1(HTLV-IIIB(MOLT-4)) of its infectivity alone to avoid virus adsorption. In contrast, HIV-1 propagated in human peripheral blood mononuclear cells (PBMC) such as HIV-1(HTLV-III(PBMC)) was more efficiently trapped by PP-PEI at lower titers as compared with HIV-1(HTLV-IIIB(MOLT-4)) from MOLT-4/HIV-1(HTLV-IIIB) cells. These data suggest host cell modification in the interactions between PP-PEI and HIV-1 strains. Since HIV-1(HTLV-IIIB(MOLT-4)) and HIV-1(HTLV-IIIB(PBMC)) were almost electrically neutral and negative, respectively, we concluded that the divergent effect of PEI on each HIV-1(HTLV-IIIB) resulted from their different electrical characteristics.