Biomedical subjects

Y Ohara

Publications and source records attributed to Y Ohara.

At least 73 records · Page 4Linked to original sources

PubMed1995

Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-beta 1.

The promoter region of the endothelial cell nitric oxide synthase (ecNOS) gene contains potential response elements for transforming growth factor-beta 1 (TGF beta 1). TGF beta 1 plays an important role in the pathogenesis of atherosclerosis, vascular hypertrophy, and angiogenesis. We therefore sought to determine whether TGF beta 1 might modulate ecNOS expression in bovine aortic endothelial cells (BAEC). TGF beta 1 increased ecNOS mRNA in a dose-dependent manner. TGF beta 1 also increased ecNOS protein content. The production of nitrogen oxides (NOx), assessed by chemiluminescence, and nitric oxide synthase activity, assessed by arginine/citrulline conversion were increased in TGF beta 1-treated cells. Transcriptional activity of the 5'-flanking promoter region of the ecNOS gene was increased by TGF beta 1, as assessed by transfection with promoter/luciferase constructs. Deletion analysis suggested that the TGF beta 1-response element was present between nucleotides -1269 and -935 from the first transcription start site, in which a putative nuclear factor-1 (NF-1) binding site existed. Gel shift assays showed that nuclear protein(s), immunologically similar to CCAAT transcription factor/NF-1, bound to the putative NF-1 binding site in a sequence-specific manner. Mutation of the putative NF-1 binding site in the promoter/luciferase construct significantly decreased the responsiveness to TGF beta 1. In conclusion, TGF beta 1 increases ecNOS expression associated with an increase in production of NO in BAEC. This response is probably mediated by transcriptional activation of the ecNOS gene promoter.

Amino Acid Oxidoreductases↗

PubMed1995

Regulation of endothelial constitutive nitric oxide synthase by protein kinase C.

Protein kinase C (PKC) plays a key role in a variety of signal transduction processes. The promoter region of the endothelial constitutive nitric oxide synthase (ecNOS) gene contains a transcriptional factor AP-1 binding element. In the present study, we sought to determine the effect of PKC inhibition on the expression of ecNOS in cultured bovine aortic endothelial cells (BAEC). The PKC inhibitor staurosporine (10 to 100 nmol/L) increased the expression of ecNOS mRNA, assessed by Northern analysis, in a dose-dependent manner. A newly developed, more specific PKC inhibitor, chelerythrine (1 to 3 mumol/L), also increased the level of ecNOS mRNA. Incubation of BAEC with phorbol 12-myristate 13-acetate (100 nmol/L) for 24 hours, which downregulates PKC, increased ecNOS mRNA expression. The protein content of ecNOS, assessed by Western analysis, was also increased in staurosporine-treated or chelerythrine-treated BAEC. The release of nitrogen oxides from staurosporine-treated or chelerythrine-treated cells both under basal conditions and in response to calcium ionophore A23187 was significantly increased (P < .05). In conclusion, the present study suggests that regulation of ecNOS is mediated by PKC. The increased release of nitric oxide induced by PKC inhibition may play a protective role against atherogenic process.

Alkaloids↗

PubMed1995

Vasoreactivity and restenosis after coronary angioplasty in the atherosclerotic pig model.

BACKGROUND: The effect of coronary angioplasty on coronary spasm remains unknown. We examined the effects of balloon angioplasty, using an oversized balloon, on coronary hypercontraction and eventual restenosis in a pig model of coronary spasm. METHODS: We performed balloon angioplasty, using an oversized balloon at the site of coronary spasm superimposed on atherosclerosis with 6 (group A, n = 14) or 1 (group B, n = 14) atmospheres of inflation pressure in miniature pigs. Using coronary angiography we assessed the coronary basal diameter and diameter change in response to histamine and serotonin before, immediately after, and 4 weeks after angioplasty. Histological examinations were performed immediately after and 4 weeks after the angioplasty. RESULTS: Before angioplasty, histamine- and serotonin-induced hypercontraction was reproducibly noted at the atherosclerotic site. Immediately after angioplasty, the coronary diameter became larger (P < 0.01) than before angioplasty in group A, but there was no significant difference in group B. The hypercontraction in group A was abolished immediately after and 4 weeks after angioplasty, whereas the hypercontraction in group B was unchanged. Histological examination revealed medial necrosis immediately after and medial fibrosis 4 weeks after angioplasty, which were more prominent in group A. Four weeks after angioplasty, the magnitude of restenosis was greater in group A than in group B. CONCLUSIONS: Angioplasty using an oversized balloon with the higher atmosphere of inflation pressure abolished coronary hypercontraction immediately after and 4 weeks after angioplasty, which probably resulted from the irreversible damage to medial smooth muscles; however, this did not prevent restenosis.

Angioplasty, Balloon, Coronary↗

PubMed1995

[Evaluation of preoperative blood preparation and blood consumption for implementation of type and screen and maximum surgical blood order schedule].

We analyzed preoperative blood preparation and intraoperative blood transfusion in Kagawa Prefectural Central Hospital and evaluated the effectiveness of maximum surgical blood order schedule (MSBOS) and Type and Screen (T&S). Forty seven kinds of surgery were performed on 1,283 cases from May, 1991 to April, 1992. Transfusion was performed in 179 cases of them. All of 1,884 units of blood that had been prepared, were crossmatched and 1,078 of them were actually transfused. The Crossmatched to Transfused ratio (C/T ratio) was 1.71. If we adopted MSBOS and T&S in 13 elective surgery, 766 units of blood and labour work for preoperative blood preparation could have been saved. MSBOS and T&S are beneficial for efficient usage of blood transfusion in surgery.

Blood Loss, Surgical↗

PubMed1994

The next generation Baylor C-Gyro Pump: antithrombogenic "free impeller" design for long-term centrifugal VAD.

The new generation centrifugal blood pump, the C2 Gyro Pump "Free Impeller Model" specifically designed for long-term ventricular assistance and a bridge to transplantation, has been developed. In the free impeller design, the impeller was completely freed from mechanical tethers by eliminating the shaft. This unique design allowed the incorporation of a center-penetrating hole in the impeller, called the center conduit, which accelerates the secondary blood flow from the bottom to the top of the impeller. During in vitro performance tests, two characteristic impeller motions, called floating mode and wandering rotational axis, were observed. In the floating mode, the impeller seemed to be floating without touching the pump casing and resulted in the idea of no bearing contact. Also, the rotational axis of the impeller exhibited a small circular motion and illustrated the idea of no stationary area in the blood path. These three characteristics are expected to be advantageous for anti-thrombogenicity and low hemolysis which are essential for a long-term centrifugal VAD.

Equipment Design↗

PubMed1994

Cardiopulmonary bypass with Nikkiso and BioMedicus centrifugal pumps.

In our department, a new compact and atraumatic centrifugal pump, Nikkiso, was developed as a second-generation cardiopulmonary bypass pump. To assess and confirm the function and controllability of this pump, comparative studies of cardiopulmonary bypass with Nikkiso and BioMedicus centrifugal pumps were performed using calves. Both pumps provided pump flows of 60-70 ml/kg/min without incidence. The hemodynamics of both groups were stable and within the normal range, and no leakage or thrombus formations were observed in either pump. All hematology and biochemistry data showed no significant differences between the two groups. Plasma free hemoglobin values of the Nikkiso pump tended to be lower than those of the BioMedicus pump. The Nikkiso pump was easy to handle because of its smaller size, and air removal was easily performed because of its low priming volume. The Nikkiso pump demonstrated easy manipulation and good controllability. This compact, atraumatic centrifugal pump meets the requirements for a second-generation cardiopulmonary bypass pump.

Animals↗

PubMed1994

An ultimate, compact, seal-less centrifugal ventricular assist device: Baylor C-Gyro pump.

We have developed a compact, seal-less, all-purpose centrifugal pump, the Baylor C-Gyro pump, which is intended as a long-term ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. In attaining this goal, we began with eliminating the shaft seals by adopting a pivot bearing system at the impeller shaft. In addition, a ring magnet encased in the bottom of the impeller was coupled magnetically to a driver magnet placed outside the pump housing (C1 Prototype). This first model yielded satisfactory performance in vitro with a flow rate of 8 L/min against 250 mm Hg at 2,400 rpm, and an index of hemolysis (IH) of 0.0083 g/100 L using bovine blood. In the second model, the C1 Eccentric Inlet Port Model, the inlet bearing support bar in the prototype were eliminated without reducing the prototype's performance. These designs for antithrombogenicity are being tested by the first in vivo experiment, which has lasted for more than 2 weeks.

Animals↗

PubMed1994

Internal hydraulic loss in a seal-less centrifugal Gyro pump.

A new index "loss factor Z" defined by Eq. 1 was introduced as the absolute expression of the mock loop resistance for testing a nonpulsatile pump. [formula: see text] where gamma is specific gravity of the fluid, g is the acceleration of gravity, delta P is total pressure head, and Q is flow. Z is expected to be constant, regardless of the pumping parameters. Z values obtained in the same mock loop but with different rotary blood pumps were almost identical and were defined as Z0. New methods of analysis of the flow-restrictive conditions of various rotary blood pumps are proposed in this paper: namely, differential loss factor delta Z, and loss factor sensitivity delta Z/delta A. The proposed Z-Q curves demonstrated better performance mapping than the conventional delta P-Q curves. Delta Z is the difference between the Z-Q curves of two different pumps. A is a design parameter of the pump; therefore delta Z/delta A is a quantitative expression of the effect of the design change on the hydraulic performance. These various indices were used to analyze the internal hydraulic loss of a centrifugal pump (Gyro pump). The relationship between its gap size (rotor casing) and hydraulic performance was assessed quantitatively by these indices. In this paper, the derivation processes and above-mentioned indices are described.

Assisted Circulation↗

PubMed1994

Successful thermal management of a totally implantable ventricular assist system.

Thermal management of the implantable ventricular assist system (VAS) is important not only from the pathophysiological point of view but also from the standpoint of system endurance. The heat distribution within the Baylor VAS was measured using different motor housing materials and environmental conditions. The temperature of the circulating water in the mock loop was set at 37 degrees and 42 degrees C. A polycarbonate motor housing was not a suitable material because of the high temperature development in the actuation system. An anodized aluminum housing demonstrated excellent heat conductivity. The surface temperature of this motor housing was 41.6 degrees C when immersed in circulating water at 42 degrees C. Heat conduction from the motor to the circulating blood revealed an effective thermal path. In the worst case, the heat flux of the motor to the circulating blood revealed an effective thermal path. In the worst case, the heat flux of the motor housing was calculated to be less than 0.062 W/cm2--an acceptable level for the surrounding tissues.

Equipment Design↗

PubMed1994

In vitro and in vivo validation tests for total artificial heart.

Properly planned in vitro and in vivo studies are mandatory to validate blood pump performance. However, standard procedures for in vitro and in vivo tests of total artificial heart (TAH) performance still do not exist. At Baylor College of Medicine, standard tests procedures for performance validation of the totally implantable TAH have been established. In this paper, these in vitro tests protocols (performance mapping tests, accelerated endurance test, hemolysis test, flow visualization tests, etc.) are described as well as in vivo test procedures (TAH implantation procedure, including surgical technique, postoperative management and tests, etc.). In addition, pathological protocols are presented. In our experience, these procedures are very simple, easy to perform, and inexpensive. These protocols are proposed as standard in vitro and in vivo tests for a TAH.

Animals↗

PubMed1994

Flow visualization in the Baylor total artificial heart.

To analyze the flow patterns of the left and right blood chambers of the total artificial heart (TAH), flow visualization studies were performed. Two setup levels were used for the flow visualization studies. For estimating the global flow patterns, the pumps were illuminated using incandescent light, and the patterns were recorded by either videotape or photography. To evaluate sectional flow patterns, a laser light was applied, and the pump could be scanned segmentally. The flow patterns were recorded by a high-speed camera. A signal was also used that synchronized the timing of the camera shutter to the pusher-plate movement signal. In the left pump chamber, major stagnations were observed in the middle area of the inflow site. To solve this problem, a modification was made that changed the inflow direction appropriately. After evaluation of the inflow port direction, a proper flow pattern was obtained, which was validated by a global flow visualization study. Furthermore, both pump chambers indicated excellent flow patterns as obtained by a segmental flow visualization study method utilizing a laser light. The Baylor TAH demonstrated excellent flow patterns in flow visualization studies, with antithrombogenicity expected. These flow visualization studies are very useful not only for validations of global flow patterns but also for validations of local areas of stagnation in various blood pumps.

Equipment Design↗

PubMed1994

Totally implantable total artificial heart and ventricular assist device with multipurpose miniature electromechanical energy system.

A multipurpose miniature electromechanical energy system has been developed to yield a compact, efficient, durable, and biocompatible total artificial heart (TAH) and ventricular assist device (VAD). Associated controller-driver electronics were recently miniaturized and converted into hybrid circuits. The hybrid controller consists of a microprocessor and controller, motor driver, Hall sensor, and commutation circuit hybrids. The sizing study demonstrated that all these components can be incorporated in the pumping unit of the TAH and VAD, particularly in the centerpiece of the TAH and the motor housing of the VAD. Both TAH and VAD pumping units will start when their power line is connected to either the internal power pack or the external battery unit. As a redundant driving and diagnostic port, an emergency port was newly added and will be placed in subcutaneous location. In case of system failure, the skin will be cut down, and an external motor drive or a pneumatic driver will be connected to this port to run the TAH. This will minimize the circulatory arrest time. Overall efficiency of the TAH without the transcutaneous energy transmission system was 14-18% to deliver pump outputs of 4-9 L/min against the right and left afterload pressures of 25 and 100 mm Hg. The internal power requirement ranged from 6 to 13 W. The rechargeable batteries such as NiCd or NiMH with 1 AH capacity can run the TAH for 30-45 min. The external power requirement, when TETS efficiency of 75% was assumed, ranged from 8 to 18 W. The accelerated endurance test in the 42 degrees C saline bath demonstrated stable performance over 4 months. Long-term endurance and chronic animal studies will continue toward a system with 5 years durability by the year 2000.

Animals↗

PubMed1994

Does hematocrit affect in vitro hemolysis test results? Preliminary study with Baylor/NASA prototype axial flow pump.

The effect of hematocrit (Ht) on in vitro hemolysis test results (i.e., index of hemolysis) was evaluated using a Baylor/NASA prototype axial flow pump. Red blood cell suspensions of six different Ht (5, 10, 15, 20, 30, 40%; n = 30) were prepared and used for this evaluation. The pump was operated for 60 min under 5 L/min flow conditions, and blood samples were taken every 10 min to measure plasma free hemoglobin levels. The normalized index of hemolysis (NIH) was calculated using the regression line slope between time and plasma free hemoglobin level, and relationships between NIH and Ht or hemoglobin (Hb) were checked. NIH and Ht had a statistically significant (p < 0.0001) correlation with a coefficient of fit of 0.976, and NIH and Hb had a statistically significant (p < 0.0001) correlation with a coefficient of fit of 0.976. To reduce the effect of Ht, NIH/Ht was proposed and compared with a modified index of hemolysis (MIH), which was normalized by the Hb level of blood. NIH/Ht and MIH had a poor correlation with Ht (coefficient of fit, 0.608) and Hb (coefficient of fit, 0.577), respectively. When blood that has a wide range of Ht or Hb values is used for in vitro hemolysis tests, NIH/Ht is suggested for use as an index of hemolysis to evaluate the hemolysis characteristics of rotary blood pumps because MIH has no dimension and it requires Hb values. In contrast, NIH/Ht has a dimension of g/100 L, which is quite understandable, and it does not require measurement of Hb levels of blood; it is therefore cost-effective.

Animals↗

PubMed1994

Development and evaluation of antithrombogenic centrifugal pump: the Baylor C-Gyro Pump Eccentric Inlet Port Model.

The Baylor C-Gyro Pump Eccentric Inlet Port Models (C1E) have been developed aiming for a long-term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. The eccentric inlet port models are characterized by their unique inlet port and secondary impeller vanes. An inlet female pivot bearing, which was fixed to a supporting bar in the prototype model, is directly embedded into the ceiling of the pump casing. An inlet port is then placed off-center to avoid the bearing area, and it is angled between 0 to 90 degrees from the upright position. In addition, small secondary vanes were incorporated into the impeller bottom to accelerate the washout flow behind the impeller. These features attained design objectives proposed for higher antithrombogenicity: a seal-less pump chamber, no stationary parts in the blood path, and acceleration of the secondary flow behind the impeller. The first in vivo experiment using C1E pumps showed excellent antithrombogenicity for up to 18 days when the experiment ceased due to severe infection in the calf.

Animals↗

PubMed1994

Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation.

We tested the hypothesis that lysophosphatidylcholine (lyso-PC) could activate protein kinase C in intact vascular segments and sought to examine some of the physiological consequences of this activation. In segments of rabbit aorta, the patterns of protein phosphorylation determined by two-dimensional electrophoresis stimulated by lyso-PC and 12-O-tetradecanoylphorbol 13-acetate (TPA) were similar. Activation of protein kinase C can stimulate superoxide anion (O2-) production in other tissues, and we found that lyso-PC-treated rabbit aortas produced twofold more O2- than control vessels. Calphostin C, a potent and specific inhibitor of protein kinase C, attenuated O2- production in lyso-PC-treated vessels but had no effect in control vessels. The effect of lyso-PC on O2- production was mimicked by TPA. In separate bioassay studies, release of the endothelium-derived vascular relaxing factor (EDRF) quantified by the response of detector vessels was markedly impaired after exposure of donor rabbit aortic segments to lyso-PC. After incubation with calphostin C, EDRF release in response to acetylcholine from lyso-PC-treated donor vessels was restored significantly. Thus, lyso-PC can activate protein kinase C in intact vessels, leading to an increase in O2- production. Activation of protein kinase C by lyso-PC may also play a role in altering the release of EDRF in response to acetylcholine. Increased O2- production in response to lyso-PC may have important consequences in the atherogenic process.

Animals↗

PubMed1994

[The pathomechanisms of virus-induced demyelination].

The pathomechanisms of virus-induced demyelination have been widely studied, especially in animal models, in order to elucidate the pathogenesis of a human demyelinating disease, multiple sclerosis. The recent development of molecular biology has partially defined the genomic segment responsible for demyelination in some viruses. It is, however, still unclear, how such a segment causes demyelination. Three main issues have been addressed regarding the mechanisms of demyelination, i.e., oligodendrocyte lytic viral infection, immune-mediated demyelination with oligodendrocyte viral infection, and immune-mediated demyelination without oligodendrocyte viral infection. Immune responses of the host are, therefore, critical, as well as viral replication and propagation in virus-induced demyelination.

Animals↗

PubMed1993

Subacute panencephalitis associated with chronic graft-versus-host disease.

A unique form of subacute panencephalitis developed in a child with aplastic anemia 8 months after an allogeneic bone marrow transplantation (BMT). It was characterized by parenchymal infiltration of CD3 lymphocytes, a marked increase in the number of microglia strongly expressing HLA-DR antigens in both the gray and white matter, and diffuse degeneration of the cerebral white matter. The onset of neurological symptoms coincided with the development of chronic systemic graft-versus-host disease (GVHD). Cellular infiltrates in the CNS lesions were exclusively CD3 lymphocytes intermingled with a small number of monocytes labeled with CD68. There was a preponderance of cells of the CD45RB phenotype. The pathological changes in visceral organs were consistent with those of chronic GVHD. In addition, scrutiny of immunohistochemistry disclosed sparse infiltration of CD3 lymphocytes and diffuse gliosis in the cerebral white matter of another child with chronic GVHD who died 9 months after allogeneic BMT. These cases are suggestive of a potential risk of CNS involvement in GVHD.

Adolescent↗

PubMed1993

Phenotypes of mononuclear cell infiltrates in human central nervous system.

Using a panel of monoclonal antibodies applicable for identification of cell types in paraffin sections, the prevalence of mononuclear cell infiltrates with different phenotypes was estimated in large areas taken from 11 cases of acute and chronic inflammatory diseases in the human central nervous system. The present study clearly demonstrated a diversity of inflammatory mononuclear cell infiltrates, and the dominance of cell types in individual lesions appeared to be determined by both the nature of the diseases and the age of the lesions. The possible pathognomonic significance of a relatively high prevalence of CD4+CD45RO+ lymphocytes in acute rabies and in a convalescent stage of Japanese encephalitis and subacute sclerosing panencephalitis is discussed.

Acquired Immunodeficiency Syndrome↗