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Biomedical subjects

T Akutsu

Publications and source records attributed to T Akutsu.

At least 37 records · Page 2Linked to original sources

Rapid protein fragment search using hash functions based on the Fourier transform.

MOTIVATION: Since the protein structure database has been growing very rapidly in recent years, the development of efficient methods for searching for similar structures is very important. RESULTS: This paper presents a novel method for searching for similar fragments of proteins. In this method, a hash vector (a vector of real numbers) is associated with each fixed-length fragment of three-dimensional protein structure. Each vector consists of low-frequency components of the Fourier-like spectrum for the distances between C alpha atoms and the centroid. Then, we can analyze the similarity between fragments by evaluating the difference between hash vectors. The novel aspect of the method is that the following property is proved theoretically: if the root mean square distance between two fragments is small, then the distance between the hash vectors is small. Several variants of this method were compared with a naive method and a previous method using PDB data. The results show that the fastest one among the variants is 18-80 times faster than the naive method, and 3-10 times faster than the previous method.

Algorithms↗

Unsteady fluid dynamics of several mechanical prosthetic heart valves using a two component laser Doppler anemometer system.

Five typical mechanical heart valves (Starr-Edwards, Björk-Shiley convexo-concave (c-c), Björk-Shiley monostrut, Bicer-Val, and St. Jude Medical) were tested in the mitral position under the pulsatile flow condition. The test program included measurements of velocity and turbulent stresses at 5 downstream locations. The study was carried out using a sophisticated cardiac simulator in conjunction with a highly sensitive 2 component laser Doppler anemometer (LDA) system. The continuous monitoring of parametric time histories revealed useful details about the complex flow and helped to establish the locations and times of the peak parameter values. Based upon the nondimensional presentation of data, the following general conclusions can be made. First, all the 5 valve designs created elevated turbulent stresses during the accelerating and peak flow phases, presenting the possibility of thromboembolism and perhaps hemolysis. Second, the difference in valve configuration seemed to affect the flow characteristics; third, the bileaflet design of the St. Jude valve appeared to create a lower turbulence stress level.

Biomechanical Phenomena↗

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↗

A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

Adolescent↗

[Contamination levels to room air arising from the use of 99mTc-gas and prevention from the contamination].

99mTc-gas (TECHNEGAS) is a 99mTc-labeled micro-aerosol which is considered to have different behavior from 133Xe or 81mKr gas. In order to estimate contamination levels to room air arising from the use of 99mTc-gas, filtered expired air during administration and 1, 2, 3, 5, 10 min after the administration were collected in each polyethylene bag. Radioactivities of the polyethylene bags, used filter and the lung were measured with 3-head scintillation camera. The activity of the expired air diminished within 6-10 min and about 5% of whole discharged 99mTc-gas was released to room air. The activity of the used filter was two times of the lung. According to these results, it is recommended that the 99mTc-gas may be administrated in a exclusive room. The administrated patient and used filter must be remain in the exclusive room.

Aerosols↗

[Quantitative assessment of an increase of myocardial 99mTc-MIBI accumulation during exercise--usefulness of response rate].

The increase of myocardial 99mTc-MIBI accumulation during exercise was evaluated quantitatively, and the feasibility of response rate as a noninvasive marker of coronary stenosis was tested. Myocardial perfusion imaging with 99mTc-MIBI during exercise and at rest was performed in patients with suspected coronary artery disease. A dose of 296 MBq of 99mTc-MIBI was injected intravenously at maximal treadmill exercise, and myocardial image was obtained 90 min later (1st image). Then, 740 MBq of 99mTc-MIBI was administered at rest, and myocardial image was repeated (2nd image). These images were corrected for a decay and injected dose, and the 1st image was subtracted from the 2nd image to obtain the rest image. An increase of myocardial accumulation of 99mTc-MIBI during exercise was defined as (exercise image-rest image) x 100/rest image (response rate). A response rate of a patient with normal coronary artery was 102%, whereas a response rate in the area of severe coronary stenosis was 21% in a patients with angina pectoris. After successful PTCA to a stenosed coronary artery, a response rate increased to 75% in this patient. Coronary perfusion reserve during exercise can be assessed noninvasively by 99mTc-MIBI. Response rate of 99mTc-MIBI provides additional information to conventional perfusion imaging and may be a new marker of severity of coronary artery disease.

Biomarkers↗

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↗

Protein structure comparison using representation by line segment sequences.

This paper proposes a new comparison method of tertiary protein structures. The method consists of two parts. First, a sequence of line segments which approximates each tertiary protein structure is computed. Then, an alignment of the sequences of line segments corresponding to input structures is computed. The proposed method is considered as an intermediate one between two comparison methods: a method based on topology diagram and a method based on structure alignment. Moreover it takes less CPU time than structure alignment methods because most structures are represented by means of sequences of at most 100 line segments. The effectiveness of the method is confirmed through a comparison with a previous method and an application to database searching for similar structures.

Algorithms↗

[Immunochemiluminometric assay (Automated Chemiluminescence System ACS: 180) for CEA].

We examined Automated Chemiluminescence System ACS: 180 for CEA assay, especially about confidence of the functional sensitivity. Serum CEA levels of normal subjects and patients were measured not only with ACS: 180 but also with immunoradiometric assay (CEA kit [Daiichi] II). Using ACS: 180 assay for CEA, intra-assay coefficients of variation (C.V.s) were 4.06% at 1.97 ng/ml, 1.62% at 17.3 ng/ml, and 2.28% at 81.3 ng/ml. Interassay C.V.s were 4.02% at 1.99 ng/ml, 1.21% at 16.5 ng/ml, and 3.44% at 79.4 ng/ml. The detection limit (functional sensitivity) of ACS: 180 assay for CEA was 0.4 ng/ml by the precision profile. The coefficient of correlation of 164 sera, which CEA values were among 0.4-100 ng/ml (working range of ACS: 180), between with ACS: 180 and with CEA kit [Daiichi] II was R = 0.942, y = 1.07 x +0.09 (p < 0.05). Seven (13.2%) normal subjects (n = 53) and 45 (34.1%) patients with malignant diseases (n = 132) had higher serum CEA levels than the cut off value (2.5 ng/ml). The sera of 82 malignant patients who had both pre- and post-operation sample were determined. Sixty-five patients of them were decrease after operation. These results of ACS: 180 resembled to that of CEA kit [Daiichi] II. We conclude that ACS: 180 for CEA assay was precise enough to measure below the cut off value, and had good performance of its speed (short incubation) and convenience.

Carcinoembryonic Antigen↗

[Investigation of discrepancy between 99mTc-HMPAO and 133Xe rCBF SPECT; a comparative study with X-ray CT findings].

To investigate the discrepancy between 99mTc-hexamethylpropyleneamine oxime (HMPAO) and 133Xe rCBF SPECT, the findings of thirty patients with reasonable rCBF reduction on 133Xe SPECT were compared with HMPAO SPECT and X-ray CT. The subjects did not include the cases of acute and subacute CVD. Both SPECT were performed within two weeks by ring-type dynamic SPECT (HEADTOME, Simadzu, Japan). In comparison between the SPECT findings by 133Xe and 99mTc-HMPAO, the subjects were classified into three groups as follow. Group A: Similar findings in the both SPECT were noted in 6 cases (20%). Group B: Smaller findings on HMPAO SPECT than that by 133Xe were in 11 cases (37%). Group C: No findings of rCBF reduction on HMPAO SPECT were in 13 cases (43%). The rCBF of the lesion measured by 133Xe SPECT in the group C was 24-35 ml/100 g/min. The density of HMPAO in the lesion did not correlate with the rCBF value. Only the severity of CT findings tend to correlate with the density of HMPAO. These results suggest that the reduction of HMPAO density depends directly on some kind of neural injury rather than the rCBF value. The injury may be caused by the flow reduction under the threshold of each neural cell. So the correlation between HMPAO density and actual rCBF might show like sigmoid curve. Then the HMPAO SPECT might directly reflect the regional extraction and fixation ratio, and the reduction of blood flow cause the minute neural-injury in the lesion of moderately reduced rCBF.

Brain↗

Effect of sodium taurodihydrofusidate on nasal drug delivery: differences in its concentration and penetrant molecular weight.

The effect of sodium taurodihydrofusidate (STDHF) on drug permeation across nasal mucosa was studied in vitro using Ussing type diffusion chamber. Disodium cromoglicate (DSCG, M.W. 512.3) and fluorescein isothiocyanate-dextran (FD) of different molecular weights (M.W. 4400-71200) were used as model drugs. Permeation profiles of DSCG and FDs showed a typical pseudo steady-state curve with short lag time. The permeability coefficient of FD (M.W. 9400) sigmodially increased with increasing STDHF concentration. It also enhanced the DSCG permeation. Interestingly the enhancement efficacy was independent of molecular weight of penetrants.

Adjuvants, Pharmaceutic↗

In vitro evaluation of platelet/biomaterial interactions in an epifluorescent video microscopy combined with a parallel plate flow cell.

Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer-coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 microM). This system permitted real-time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether-polyurethanes (SPEUs), PU-PTMG(650) and PU-PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s-1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real-time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma beta-thromboglobulin (beta-TG) levels were also measured before and after each run. PU-PTMG(650) showed a significantly higher number of adhered platelets than PU-PTMG(2000) at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Pulsatile flow and simple flow control method during weaning period in centrifugal pump: toward more expanded usage in open heart surgery.

To expand the usage of the centrifugal pump (CP) in open heart surgery, we performed two studies. In the first, we evaluated pulsatile flow in the CP. In vitro pump performance of the Terumo Capiox pump (TCP) and the Sarns Delphin pump (SDP) and increase of free hemoglobin (mg/dl) after driving 6 h were investigated using bovine blood. A roller pump (RP) was used as a comparison. Equally effective pulsatile flow was obtained in both CPs. Hemolysis was less severe in TCP (120 mg/dl) than SDP (210 mg/dl) and RP (320 mg/dl). In the second study, we evaluated a simple flow control method. Flow rate was easily controlled with step-wise clamping of 3-pronged tubing (Triple-flow) without changing rotational speed, regardless of afterload. Fluctuation of flow was much less with this method than with the rotational speed change method. The use of pulsatile flow of TCP, with its minimum increase of hemolysis and the easier flow control method during the weaning process, may expand the usage of CP in open heart surgery.

Animals↗

[Xenon-133 rCBF SPECT by newly designed bolus inhalation method].

Single photon emission computed tomography (SPECT) with 133Xe gas inhalation method enables measurement of regional cerebral blood flow (rCBF) quantitatively. But this method is inferior to the method with 99mTc-HMPAO or 123I-IMP in the quality of images. Efficient administration of 133Xe gas more than usual is supposed to improve quality of SPECT images. In this study we designed bolus inhalation method, a new method to efficiently administer 133Xe gas of usual dose (1,850 MBq), and examined its fundamental aspects and clinical feasibility. The method was initiated by bolus administration of 133Xe gas synchronously in inspiration phase via a small tube connected to a mouthpiece and was followed by steady breathing of the gas in a closed circuit with a spiro-bag. Introduction of this method provided almost twofold increase in count ratio at the head in comparison with a conventional inhalation method. Consequently, considerable improvement in the quality of rCBF images was achieved by optimization of a reconstruction filter of SPECT.

Administration, Inhalation↗

Chronic effects of a cardiac assist device on the bulk and regional mechanics of the failed left ventricle in goats.

Pneumatically driven, diaphragm-type left ventricular assist devices (LVADs) were implanted into 8 goats with profound induced infarction to the left ventricle by using multiple ligations of the left anterior descending (LAD) coronary artery as well as small arteries in the LAD distribution area. Left ventricular diameters, regional myocardial segment lengths, and wall thicknesses were measured by sono-micrometers. After left ventricular function seemed to be recovered, the goats were weaned off the LVADs after a gradual decrease of pump bypass flow over several days. Thereafter, hemodynamic and cardiac parameters were observed for about 1 month more. Three animals recovered successfully owing to the LVAD pumping. Before starting pump-weaning procedures, the bulk mechanical work (BMW) done by the left ventricle during LVAD pumping and under temporary pump-off conditions was 0.08 +/- 0.01 (mean +/- SE) and 0.22 +/- 0.01 W/100 g left ventricular weight (LVW), respectively, while the regional mechanical work done by the normal myocardium (RMWn) was 1.5 +/- 0.4 and 4.3 +/- 0.9 mW/cm3 during pumping and under temporary pump-off conditions, respectively. BMW and RMWn values obtained under pump-on conditions both increased gradually during the weaning process. Even after pump removal, they continued to increase and reached constant values of about 0.3 W/100 g LVW and 10 mW/cm3, respectively, around 2 weeks after pump removal. Although the myocardium in the infarction area did no work for the first several days after surgery, it recovered to do some external work with the aid of LVAD pumping. However, recovery of left ventricular function owed more to compensatory increases in pumping ability of the remaining normal myocardium than to recovery of the damaged myocardium. The LVAD could salvage severely damaged hearts unless the infarction area exceeded 50% of the left ventricular wall.

Animals↗

A straight path centrifugal blood pump concept in the Capiox centrifugal pump.

This article describes comparative studies of a newly developed "straight path" centrifugal pump (Capiox centrifugal pump) targeted for open-heart surgery and circulatory support. A unique straight path design of the rotor was very effective in reducing the pump's rotational speed and prime volume. This pump was evaluated for hydraulics, hemolysis, depriming characteristics, cavitation, and heat generation. Two commercially available centrifugal pumps, the Biomedicus cone-type pump and the Sarns 3M impeller-type pump, were used as controls. The new pump required the lowest pump speed to produce the same flow rates under the same pressure loads and demonstrated the lowest hemolysis and the lowest temperature rise with the outlet clamped. The air volume required to deprime the new pump was one-third to one-half that for the other pumps, and no sign of cavitation was observed even if a small amount of air was introduced to the pump inlet under a negative pressure of 200 mm Hg.

Animals↗