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T Nishinaka

Publications and source records attributed to T Nishinaka.

At least 37 records · Page 2Linked to original sources
PubMed1999

In vivo evaluation of the national cardiovascular center electrohydraulic total artificial heart.

We have been developing an electrohydraulic total artificial heart system. The system comprises an intrathoracic pumping unit composed of diaphragm type ellipsoidal blood pumps and an energy converter in addition to an electronics unit. The in vivo performance of the pumping unit was evaluated in a series of animal implantations with 3 calves weighing 62-85 kg. An interatrial shunt 4.5 mm in diameter was made in the atrial septum to compensate left-right imbalance. Two calves died early postoperatively, one of external controller power failure and the other of interatrial shunt stenosis due to thrombus formation. One calf, however, survived over 10 days under stable circulatory conditions. No abnormality was found in the oxygen metabolic condition or in major organ functions. The generation and dissipation of heat from the device was acceptable. This animal died of device malfunction caused by energy converter bearing breakdown. The device demonstrated a good anatomic fit without compromising the great vessels and adjacent tissues. It is concluded that the pumping unit has a sufficient in vivo basic performance although appropriate countermeasures are to be implemented against the detected problems concerning mechanical durability and interatrial shunt patency.

Animals↗
PubMed1999

Cardiac autonomic nervous function during long-term nonpulsatile left heart bypass.

We investigated the changes in cardiac autonomic nervous activities during long-term nonpulsatile left heart bypass (NLHB) by analyzing heart rate variability. A pulsatile ventricular assist device was installed in 3 goats, and pulsatile left heart bypass (PLHB) was conducted for 2 weeks. Then, NLHB was maintained for the following 4 weeks. The segmental data of the R-R intervals (R-Rs) was analyzed by maximum entropy spectral analysis. Changes in evaluated parameters from the last week of PLHB to the 4th week of NLHB were as follows: the mean R-Rs increased from 511 ms to 692 ms; the coefficient of variation of R-R increased from 10.2 to 14.1%; the power of the low frequency band (LF) increased from 747 ms2 to 2,855 ms2; the power of the high frequency band (HF) increased from 512 ms2 to 1,270 ms2; and the ratio of LF to HF increased from 2.6 to 6.5. These results indicated that the cardiac autonomic nervous activity, both sympathetic and parasympathetic, increased during long-term NLHB.

Analysis of Variance↗
PubMed1999

Development of an ultracompact integrated heart-lung assist device.

A novel integrated heart-lung assist device has been developed as a simple to use portable cardiopulmonary support system. The device comprises a centrifugal pump and an artificial lung, which is located around the pump, in an all in one system. The special membrane employed precludes plasma breakthrough in protracted use and enables preprimed setup. Test lungs consisting of the same membrane preserved gas exchange function well after 3 months of preprimed storage. The entire blood contacting surface is treated with covalent heparin bonding to impart good antithrombogenicity. Heparin bonded test lungs could be continuously perfused without systemic anticoagulation as long as 36 days in a venoarterial bypass chronic animal study using goats. The prototype device (diameter, 126 mm; height, 59 mm; membrane area, 0.85 m2; priming volume, 180 ml) demonstrated 9 L/min pump output at a 400 mm Hg pressure head and 180 ml/min oxygen and 110 ml/min carbon dioxide transfer rates at 5 L/min blood flow. We conclude that this device has potential to be the next generation cardiopulmonary support system.

Animals↗
PubMed1999

Diminished vasoconstrictive function caused by long-term nonpulsatile left heart bypass.

We investigated the functional changes of the systemic vascular system due to prolonged nonpulsatile left heart bypass (NPLHB). Three adult goats underwent pulsatile left heart bypass (PLHB). Two weeks later the PLHB was changed to the NPLHB, which was conducted for 4 weeks. The aortic pulse pressure was 39 and 16 mm Hg during the PLHB and NPLHB, respectively. Systemic vascular resistance (SVR) and the plasma norepinephrine level were measured at the end of PLHB (PUL), and in the 1st, 2nd, 3rd, and 4th weeks of NPLHB (NP1w, NP2w, NP3w, and NP4w). At each point, 1 microg/kg norepinephrine was injected, and the elevation of the SVR (deltaSVR) was calculated. The SVR and the plasma norepinephrine level did not change significantly during the entire course. However, deltaSVR decreased during NPLHB and became significantly lower at NP3w and NP4w than that at PUL (NP3w: 839 +/- 164, NP4w: 746 +/- 268, and PUL: 1,239 +/- 324 dyne x s x cm(-5)). These results strongly indicated that prolonged NPLHB significantly diminished the constrictive function of the vascular system.

Animals↗
PubMed1999

Augmentative effect of pulsatility on the wall shear stress in tube flow.

Wall shear stress (WSS) has been considered to play an important role in the physiological and metabolic functions of the vascular endothelial cells. We investigated the effects of the pulse rate and the maximum flow rate on the WSS to clarify the influence of pulsatility. Water was perfused in a 1/2 inch transparent straight cylinder with a nonpulsatile centrifugal pump and a pulsatile pneumatic ventricular assist device (VAD). In nonpulsatile flow (NF), the flow rate was changed 1 to 6 L/min by 1 L/min increments to obtain standard values of WSS at each flow rate. In pulsatile flow (PF), the pulse rate was controlled at 40, 60, and 80 bpm, and the maximum flow rate was varied from 3.3 to 12.0 L/min while the mean flow rate was kept at 3 L/min. The WSS was estimated from the velocity profile at measuring points using the laser illuminated fluorescence method. In NF, the WSS was 12.0 dyne/cm2 at 3 L/min and 33.0 dyne/cm2 at 6 L/min. In PF, the pulse rate change with the same mean, and the maximum flow rate did not affect WSS. On the other hand, the increase in the maximum flow rate at the constant mean flow rate of 3 L/min augmented the mean WSS from 13.1 to 32.9 dyne/cm2. We concluded that the maximum flow rate exerted a substantial augmentative effect on WSS, and the maximum flow rate was a dominant factor of pulsatility in this effect.

Blood Flow Velocity↗
PubMed1999

Imaging the RecA-DNA complex by atomic force microscopy.

Atomic force microscopy (AFM) was applied to study the RecA protein and its complexes with DNA in air and in aqueous solution. RecA and DNA were reacted under several conditions, and deposited onto a mica substrate pre-treated in various ways. We found that the structure of the RecA and RecA-DNA complexes, especially the height of the molecules, was affected by the sample preparation method such as gel filtration, and environment during imaging.

Bacteriophage M13↗
PubMed1999

Prolonged nonpulsatile left heart bypass diminishes vascular contractility.

We investigated possible functional changes in the vascular system accompanying the morphological change in prolonged nonpulsatile left heart bypass (LHB). Three adult goats underwent pulsatile LHB. Two weeks postoperatively, the pulsatile ventricular assist device was replaced with a centrifugal pump and nonpulsatile LHB was subsequently conducted for 4 weeks. The mean aortic pulse pressure was 39 and 16 mmHg during the pulsatile and nonpulsatile LHB, respectively Systemic vascular resistance (SVR) and plasma norepinephrine levels were measured at the end of pulsatile LHB (PUL), and at the end of 1st, 2nd, 3rd, and 4th week of nonpulsatile LHB (NP1w, NP2w, NP3w, NP4w, respectively). At each point, 50 microg/kg nitroglycerin and 1 microg/kg norepinephrine were injected and the minimal and maximal values of SVR after injection were calculated as parameters reflecting the vascular tonus and contractility. The SVR and plasma nor epinephrine level did not significantly change during the entire course (SVR: 1106, 895, 982, 920, and 938 dyne x sec x cm(-5); norepinephrine level: 0.3, 0.2, 0.1, 0.2, and 0.1 ng/ml; at PUL, NP1w, NP2w, NP3w, and NP4w, respectively). The minimal value of SVR after nitroglycerin injection remained unchanged, indicating that vascular tonus was stable during the entire course (618, 687, 623, 560, 653 dyne x sec x cm(-5), respectively). In contrast, the maximal value of SVR after norepinephrine injection at NP3w and NP4w (1695 and 1759 dyne x sec x cm(-5)) became significantly reduced compared to that at PUL (2346 dyne x sec x cm(-5)). These results indicated that prolonged nonpulsatile left heart bypass did not affect the vascular tonus, but significantly diminished the vascular contractility.

Animals↗
PubMed1998

Base pair switching by interconversion of sugar puckers in DNA extended by proteins of RecA-family: a model for homology search in homologous genetic recombination.

Escherichia coli RecA is a representative of proteins from the RecA family, which promote homologous pairing and strand exchange between double-stranded DNA and single-stranded DNA. These reactions are essential for homologous genetic recombination in various organisms. From NMR studies, we previously reported a novel deoxyribose-base stacking interaction between adjacent residues on the extended single-stranded DNA bound to RecA protein. In this study, we found that the same DNA structure was induced by the binding to Saccharomyces cerevisiae Rad51 protein, indicating that the unique DNA structure induced by the binding to RecA-homologs was conserved from prokaryotes to eukaryotes. On the basis of this structure, we have formulated the structure of duplex DNA within filaments formed by RecA protein and its homologs. Two types of molecular structures are presented. One is the duplex structure that has the N-type sugar pucker. Its helical pitch is approximately 95 A (18.6 bp/turn), corresponding to that of an active, or ATP-form of the RecA filament. The other is one that has the S-type sugar pucker. Its helical pitch is approximately 64 A (12.5 bp/turn), corresponding to that of an inactive, or ADP-form of the RecA filament. During this modeling, we found that the interconversion of sugar puckers between the N-type and the S-type rotates bases horizontally, while maintaining the deoxyribose-base stacking interaction. We propose that this base rotation enables base pair switching between double-stranded DNA and single-stranded DNA to take place, facilitating homologous pairing and strand exchange. A possible mechanism for strand exchange involving DNA rotation also is discussed.

Base Pairing↗
PubMed1998

A retinoblastoma susceptibility gene product, RB, targeting protease is regulated through the cell cycle.

Degradation of cyclin B and cyclin-dependent kinase inhibitor, p27, at a specific time has been shown to play a critical role in regulating the cell cycle. SPase, a nuclear and cytosol protease with cathepsin B- and L-like proteolytic activity, has been identified in several cell lines. This proteolytic enzyme selectively degraded nuclear proteins such as retinoblastoma susceptibility gene product, RB, and transcription factor, SP-1. High levels of SPase activity were detected at the G1/S, moderate levels at the G1 and S phases, and undetectable activity at the M phase of synchronized CV-1 cells, suggesting that SPase activity is regulated through the cell cycle. Degradation of RB correlated with SPase activity throughout the cell cycle, suggesting that SPase regulates RB, which has a functional role in regulating cell cycle. These results demonstrated that SPase plays an integral role in regulating the nuclear regulator, RB, in controlling cell cycle progression.

Animals↗
PubMed1998

Afterload-dependent flow fluctuation of centrifugal pump: should it be actively fixed?

To evaluate the clinical meaning and effects of afterload-dependent flow fluctuation in a centrifugal pump, concomitant measurement of flow rate and mixed venous oxygen saturation (SVO2) was performed in 5 cases of open heart surgery in which the patients underwent cardiopulmonary bypass (CPB) with the Terumo Capiox centrifugal pump. Continuous measurement of SVO2 using the 3M CDI System 100 was performed with a disposable cuvette incorporated into the drainage circuit. After the target flow rate of 2.4 L/min/m2 was obtained under a nonbeating condition, the pump rotational speed was fixed. During the cooling and low temperature period, SVO2 decreased as the flow rate spontaneously decreased but still stayed around 80% even with a 15-20% decrease in blood flow rate. This indicates that a luxury perfusion condition is ensured as long as the body temperature is kept low. In contrast, during the rewarming period, SVO2 decreased to around 70-75% despite a 15-25% spontaneous increase in flow rate. Although this level of SVO2 still indicates adequate systemic perfusion, there is a possibility of regional hypoperfusion in patients with such conditions as cerebrovascular disease. In conclusion, although diligent adjustment of the physiological fluctuating flow rate in the centrifugal pump seems unnecessary during conventional open heart surgery, manual control may be necessary especially during the rewarming period, normothermic surgery, or circulatory assist for shocked patients. From this study, we also conclude that the major benefit of the afterload-independent autoflow control system of the centrifugal pump is the improvement of safety in terms of the fixed reservoir level and the handling of cardiopulmonary bypass.

Blood Flow Velocity↗
PubMed1997

An extended DNA structure through deoxyribose-base stacking induced by RecA protein.

The family of proteins that are homologous to RecA protein of Escherichia coli is essential to homologous genetic recombination in various organisms including viruses, bacteria, lower eukaryotes, and mammals. In the presence of ATP (or ATPgammaS), these proteins form helical filaments containing single-stranded DNA at the center. The single-stranded DNA bound to RecA protein is extended 1.5 times relative to B-form DNA with the same sequence, and the extension is critical to pairing with homologous double-stranded DNA. This pairing reaction, called homologous pairing, is a key reaction in homologous recombination. In this NMR study, we determined a three-dimensional structure of the single-stranded DNA bound to RecA protein. The DNA structure contains novel deoxyribose-base stacking in which the 2'-methylene moiety of each deoxyribose is placed above the base of the following residue, instead of normal stacking of adjacent bases. As a result of this deoxyribose-base stacking, bases of the single-stranded DNA are spaced out nearly 5 A. Thus, this novel structure well explains the axial extension of DNA in the RecA-filaments relative to B-form DNA and leads to a possible interpretation of the role of this extension in homologous pairing.

Base Composition↗
PubMed1997

A unique cathepsin-like protease isolated from CV-1 cells is involved in rapid degradation of retinoblastoma susceptibility gene product, RB, and transcription factor SP1.

The regulation of transcription factors by kinase or phosphatase has been well-described. However, little is known about the inactivation of transcription factors or the nuclear regulators by proteolytic degradation. In this report, we purified a specific protease, SPase, from nuclear extracts of the green monkey kidney cell line, CV-1. Studies of biochemical characteristics and substrate specificity indicated that SPase is a cathepsin B-like cysteinyl protease. However, the two tryptic peptide sequences derived from the purified SPase are either identical or highly homologous to those of human cathepsin L, and furthermore, SPase shares immunoreactivity with both anti-human cathepsin L and anti-mouse cathepsin L antibody. The SPase was shown to be localized in both cytoplasm and nucleus when subcellular compartments of CV-1 cells were fractionated. Transcription factor, SP1, and retinoblastoma susceptible gene product, RB, are substrates of SPase while other nuclear factors such as c-Jun and c-Fos are not. These results implied that SPase plays an integral role in regulating a set of proteins in the nuclei. In vivo treatment of CV-1 cells with cysteinyl protease inhibitor, E-64d, protected RB from degradation. SPase failed to degrade underphosphorylated RB present in TPA induced terminally differentiated HL-60 or U937 cells. Phosphorylation of RB may cause conformational changes, thus facilitating proteolytic digestion. These observations suggest that an alternative pathway inactivates the function of RB in controlling cell growth. Therefore, a possible role of SPase may be to affect the stability of important regulators involved in controlling cellular proliferation and differentiation.

Amino Acid Sequence↗
PubMed1997

Clinical evaluation of pulsatile flow mode of Terumo Capiox centrifugal pump.

The Terumo Capiox centrifugal pump system possesses an automatic priming function in which the motor repeatedly stops and runs intermittently to eliminate air bubbles in the circuit through the micropores of the hollow-fiber membrane oxygenator. By modifying this mechanism, we have developed a pulsatile flow mode. In this mode, maximum and minimum pump rotational speeds can be independently set every 20 rpm in the range of 0 to 3,000 rpm. The duration of the pump run at maximum and minimum speeds can also be independently set every 0.1 s in the range of 0.2 to 15 s. In a clinical trial, after obtaining the desired flow rate, 2.4 L/min/m2 in nonpulsatile flow mode, a pulsatile flow mode of 60 cycles/min (with 1 cycle being maximum speed for 0.4 s and minimum speed for 0.6 s) was obtained by adding and subtracting 500 rpm to and from the rotational speed in nonpulsatile flow mode. Pulse pressures in the femoral artery and in the circuit just proximal to the perfusion cannula (6.5 mm Sarns high flow cannula with metal tip) were measured in 5 patients who underwent pulsatile cardiopulmonary bypass (CPB) for a coronary artery bypass graft (CABG), and compared to pulse pressures obtained by intraaortic balloon pumping (IABP) in 3 patients and by the pulsatile mode of the 3M Delphin pump in 3 patients. The platelet count, free hemoglobin, and beta-thromboglobulin (beta-TG) were measured and compared with measurements from another 5 patients who underwent nonpulsatile CPB. Although the pulse pressure measured in the circuit was 180 mm Hg on average, the pressure in the femoral artery was only 15 to 40 mm Hg with a mean of 20 mm Hg. In the same patients, 60 to 80 mm Hg pulse pressure was obtained with IABP. The pulse pressure obtained with the Delphin pump was not more than that obtained with the Terumo pump. There were no significant differences in percents of preoperative levels of platelet counts (pulsatile, 87.6 +/- 15.8% and nonpulsatile, 72.4 +/- 40.6%), free hemoglobin (pulsatile, 18 +/- 8 mg/dl and nonpulsatile, 25 = 7 mg/dl), and beta-TG (pulsatile 298 +/- 28 ng/ml and nonpulsatile, 312 +/- 143 ng/ml). In conclusion, although the pulsatile mode of the Terumo centrifugal pump did not exhibit any adverse effects hematologically, the pulse pressure obtained was unsatisfactorily small, mainly because of dumping caused by the perfusion cannula.

Angina Pectoris↗
PubMed1997

Hypertrophic obstructive cardiomyopathy with abnormalities of the mitral valve complex.

The mechanism of obstruction of the left ventricular outflow tract (LVOT) in hypertrophic obstructive cardiomyopathy (HOCM) is mainly due to dynamic systolic anterior motion (SAM) of the mitral valve. We report a case of HOCM with mitral regurgitation (MR) associated with complicated abnormalities of the mitral apparatus which contributed to a high pressure gradient through the LVOT. A small, 53-year-old woman was admitted for chest pain and palpitation. Examinations revealed asymmetric septal hypertrophy of the left ventricle, MR, SAM of the mitral valve and a high pressure gradient (108 mmHg) through the LVOT. Operative findings revealed an abnormally hypertrophied interventricular septum, an extensively thickened and enlarged anterior mitral leaflet (AML), malposition of the origin of the anterior papillary muscle arising closer to the aortic annulus than normal, and its direct insertion into the AML without any distinguishable chordae tendineae. The hypertrophied septum and the large and protruding AML appeared to obstruct the LVOT, resulting in a loss of subaortic clearance that was recovered after mitral valve replacement and myectomy. Pathology of the papillary muscle was characteristic of HOCM, showing disorganization and disarray of myocardial fibers, bizarre-shaped nuclei, and intercellular fibrosis, while those of the mitral leaflets negated both rheumatic changes and endocarditis.

Cardiomyopathy, Hypertrophic↗
PubMed1997

Conformational distortion of sugar moieties in the RecA-bound DNA structure determined by a simulated annealing method.

We recently reported an NMR study indicating that the DNA structure bound to RecA protein contains a novel deoxyribose-base stacking interaction. Although the final structure calculated by the simulated annealing was well defined, the type of sugar puckers was neither pure C2'-endo nor C3'-endo, but something in between. This implies that the sugar moieties in the RecA-bound state actually take an intermediate puckering, but we can not exclude the possibility that RecA-bound DNA takes multiple conformations between the S-type and N-type of sugar puckers. In either case, the DNA structure within RecA filaments shows a unique property that is distinct from canonical DNA structures.

DNA↗
PubMed1996

Clinical application of a newly developed autoflow control system for the Terumo centrifugal pump: from external control to built-in direct control.

We have developed an autoflow control system for the Terumo Capiox centrifugal pump, the SP-101. First, we made an external control system regulated by a personal computer through a serial communications line. Although an in vivo experiment using a goat showed excellent performance in regulating the flow, a communication error that caused an abrupt and instantaneous flow fluctuation was noted occasionally. Therefore, we incorporated a check-sum function to solve this problem. After this improvement, 5 patients safely underwent cardiopulmonary bypass using a pump having this autoflow control. As the next step for more practical usage, we developed a built-in autoflow control system in which the control device is entirely incorporated into the console without a communications line. This system demonstrated better response and reliability than the external control system and was applied successfully in 3 patients. In conclusion, this autoflow mode will expand the usage of centrifugal pumps through improved handling.

Algorithms↗
PubMed1996

Less blood damage in the impeller centrifugal pump: a comparative study with the roller pump in open heart surgery.

A centrifugal pump with an impeller (Nikkiso Centrifugal Pump, Model HPM15; Nikkiso Co. Ltd.) was applied to cardiopulmonary bypass (CPB) in 14 patients who underwent elective coronary artery bypass grafting. Serum hemoglobin level, platelet count, and serum beta-thromboglobulin (beta TG) level were measured during CPB. The results were compared with those obtained in a comparative roller pump (RP) group (n = 10). There was no difference in the time on CPB between the NP (109 min) and RP (121 min) groups. The serum beta TG level (ng/ml) was lower in the NP group than in the RP group (obtained 90 min after the initiation of CPB). The plasma-free hemoglobin level also was lower in the NP group than in the RP group (obtained 90 min after the initiation of CPB, 120 min after the initiation of CPB, immediately after the termination of CPB, 3 h after termination of CPB; p < 0.01). There was no significant difference in platelet depletion. The HPM15 pump showed excellent hemodynamic performance with less blood trauma compared with the roller pump in its clinical application to open heart surgery.

Adult↗