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Biomedical subjects

T Akutsu

Publications and source records attributed to T Akutsu.

At least 19 recordsLinked to original sources

Agarose for a bioartificial pancreas.

Islets were encapsulated into 5% concentration agarose microbeads. The effect of microencapsulation on islet allograft survivals was determined using a streptozotocin-induced diabetic (STZ) mouse and a nonobese diabetic (NOD) mouse as recipients. All five STZ BALB/c mice receiving microencapsulated islets (C57BL/6) maintained normoglycemia indefinitely. When NOD mice were used as recipients of the bioartificial pancreas, four of five grafts (islets from C3H/He) functioned for more than 80 d. Two of five NOD mice maintained normoglycemia until animals were sacrificed at 102 and 192 postoperative d. Microbeads made of commercially available agarose can effectively prolong alloislets functioning in the STZ-diabetic mouse and even in the NOD mouse (animal model of human type I diabetes) without the use of any immunosuppressive drug.

Animals

Mechanism of protein folding. IV. Forming and breaking of disulfide bonds in bovine pancreatic tripsin inhibitor.

The folding mechanism of bovine pancreatic tripsin inhibitor (BPTI) is explained theoretically on the basis of the island model, where the driving force of folding is hydrophobic interaction. For this purpose, we take a look at the formation and breaking of disulfide bonds during the folding process of BPTI. The intermediate conformations and the native one are successfully obtained, which satisfy the so-called "lampshade" geometrical criterion for the formation of the disulfide bonds. The folding pathway is consistent with the renaturation experiment by Creighton. In addition, an elaborate treatment of side chains of amino acid residues by the software programme CHARMm confirms quantitatively the formation of disulfide bridges.

Animals

[Neurological and neuroimaging studies of eclampsia].

Clinical and neuroimaging studies were made in twenty-one patients during the attack of eclampsia. Most frequent neurological signs and symptoms were the impairment of consciousness, headache, seizure and visual disturbance. Mean arterial blood pressure increased by 46 mmHg (n = 21) during the attacks. Eight of 9 patients studied by CT and/or MRI showed transient abnormalities on brain images during the attack in the occipital cortex, basal ganglia, and internal and external capsule. The findings were compatible with brain edema and were seen mainly in the white matter. Cerebral blood flow measured by SPECT method in one patient during an attack with visual disturbance showed increased blood flow in the occipital cortex. Acute increase in blood pressure, cerebral hyperperfusion and edema, similar to the pathophysiology of hypertensive encephalopathy, were considered to play an important role in the pathogenesis of eclampsia.

Adult

[Effects of sodium bicarbonate on the end-tidal CO2,PaCO2, HCO3-, PH and cerebral blood flow].

To estimate the quantitative reactivity of cerebral blood flow (CBF), the effects of sodium bicarbonate on the end-tidal CO2, arterial PaCO2, HCO3-, PH and CBF were examined. The CBF was measured by 133Xe inhalation method with ring type SPECT (HEADTOME). Activation study with sodium bicarbonate administration was performed after 30 minute of resting study, and the reactivity of each parameters was investigated. The arterial HCO3- and PH increased with similar reactivity, but PaCO2, end-tidal CO2 and CBF in the non-injured hemisphere changed with irregular reactivity. The excellent correlation between PaCO2 and end-tidal CO2 was vanished by the administration of sodium bicarbonate. The reactivity of CBF did not correlate with reactivity of PaCO2 and end-tidal CO2, but correlated with arterial HCO3- and PH. Thus the measurement of arterial HCO3- and PH may be indispensable to estimate the CBF reactivity with the administration of sodium bicarbonate.

Aged

Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat.

Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change.

Animals

Long-term circulatory maintenance with a left-sided single artificial heart.

The purpose of this study is to examine the feasibility of long-term circulatory maintenance with only a left-sided single artificial heart that is inserted between the left atrium and the aorta to assist a nonfunctioning heart. The basic hemodynamics were determined in short-term experiments in goats (n = 4), and feasibility studies of long-term circulatory maintenance with a single artificial heart during cardiac arrest were performed in long-term experiments (n = 12). When pulmonary vascular resistance was less than 15,000 dynes .sec.cm-5.kg, which was twice the normal value, the circulation was well maintained with the single artificial heart alone, so long as the right atrial pressure was kept at 14 to 16 mm Hg. Under such conditions the flow yielded by the single artificial heart fluctuated between 80 and 140 ml/kg/min depending on the animal's demand, while the mean arterial pressure was kept above 80 mm Hg. The goats behaved normally, although retention of pleural effusion was a serious problem in maintaining normal circulation over a long-term. Maintaining the plasma total protein level above 6.0 gm/dl delayed the onset of retention or even prevented pooling of pleural effusion. The longest survival period to date has been 38 days. We conclude that when the pulmonary vascular resistance is less than twice the normal value and the total protein level is above 6.0 gm/dl, a left-sided single artificial heart alone can maintain normal circulation and provide time for patients with a nonfunctioning heart to undergo a further treatment, such as heart transplantation.

Animals

[Hemiplegic migraine complicated with coronary vasospasm].

There are many theories and hypotheses concerning with the pathogenesis of migraine. The clinical effectiveness of vasoactive drugs and many investigations on the cerebral blood flow in patients with migraine strongly support a vascular theory. In present paper we report a case of 26-year-old Japanese male, who suffered from hemiplegic migraine and coincidental coronary vasospasm, and discussed the pathogenesis of migraine. In October 1986, the patient developed the first attack of throbbing headache in the left temporal area with nausea and vomiting, following typical visual aura. One week later, he developed the second migrainous attack and then he felt his right extremities paralyzed and numb. Although the headache and weakness resolved within one hour, similar migrainous attack with transient hemiparesis repeated two or three times a month. Although the longest period required for resolving weakness was three days, the MRI, the CT and the electroencephalogram revealed no significant abnormality. In January 1987, during his stereotyped attack of hemiplegic migraine, he also developed oppressive feeling on his anterior chest and these symptoms resolved within fifteen minutes. Because the results of Holter electrocardiogram and ultrasound echocardiogram indicated angina pectoris, a coronary angiography was performed in February 1987. During the angiographical procedures, he began to complain of the oppressive feeling on his anterior chest, and the coronary angiography revealed the definite vasospasm in the anterior descending branch of the left coronary artery. Sublingual nitroglycerin administration resolved the vasospasm, but thereafter the patient developed his stereotyped hemiplegic migrainous attack.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ventilatory effects of percutaneous magnetophrenic stimulation.

This study was conducted with the purpose of elucidating the ventilatory effect of percutaneous magnetic stimulation of the phrenic nerve and investigating the possibility of clinically utilizing this effect as the mechanism of an artificial respirator. A magnetic stimulator consisting of a flat circular coil generating strong magnetic fields up to a maximum of 1.3 Tesla was developed. Formed from 1.8 mm diameter copper wire, this coil is 40 mm in diameter, 14 mm in thickness and has an inductance of 24 microH. The appurtenant current generator can deliver more than 5000 A to the coil. The capacitor terminal voltage (Vc) of the generator was used as a parameter of the intensity of the stimulus. Ventilatory effects were assessed mainly by diaphragmatic electromyogram and by transdiaphragmatic pressure, ventilation flow and tidal volume measurements. Magnetic stimulation was applied percutaneously to a unilateral phrenic nerve in dogs as well as human subjects and also to a median nerve of the forearm in human subjects. The range of stimulatory intensity Vc necessary to obtain ventilatory effects was 400-500 V, and the tidal volume thus obtained corresponded to normal breathing at rest for both dogs and humans. No pain was felt in the vicinity of point of application of the stimulator and there were no significant adverse effects such as changes in the ECG or heart rate. These results indicated that percutaneous magnetic stimulation of the phrenic nerve could produce adequate ventilatory effects in control applications.

Animals

Effects of cardiac assist on the bulk and regional mechanics of the ischemic left ventricle in dogs.

Pneumatically driven left ventricular assist devices (LVADs) were implanted between the left atria and the descending thoracic aortas of dogs and were counter-pulsated synchronously with the electrocardiogram at 1:1 and 2:1 duty ratios. Seven pairs of miniature sonomicrometers were implanted into the left ventricle (LV) to measure the LV muscular length and diameter. Ischemia was induced by the ligation of the left anterior descending coronary artery (LAD). Bulk and regional mechanical work were calculated from these dimensions and the left ventricular pressure. LVAD reduced the bulk work in the ischemic and normal hearts not only in the 1:1, but also in the 2:1, pumping modes. The left ventricular bulk work measured under the pump-off condition decreased progressively until around 2 h after the LAD ligation, and thereafter, it became constant. The regional myocardial work in the normal area of the ischemic heart was significantly decreased by the LVAD pumping (by 55%), whereas that in the ischemic area remained at near zero level regardless of pumping or nonpumping. The results obtained indicated that LVAD is useful not only to rest the severely damaged natural heart, but also to maintain the viability of ischemic myocardium.

Animals

Continuous in-line monitoring of oxygen delivery to control artificial heart output.

In order to evaluate the pump output control based on the oxygen delivery to peripheral tissues, arterial and mixed venous hemoglobin content ([Hb]) and oxygen saturation (SO2) were continuously monitored in three biventricular bypass animals (3-, 6-, and 40-day experiments) with fibrillating ventricles. The specially developed oxygen sensors were mounted in the outflow ports of the artificial hearts to measure [Hb] and SO2. One animal was exercised on the treadmill at 2.0 mile/h for 15 min with pump flows fixed to deliver oxygen of (a) above 13 cc/min/kg, (b) 10, and (c) 9. In (a), the mixed venous saturation (SvO2) dropped to approximately 25% with no increase in the blood lactate level. In (b) and (c), the SvO2 decreased to approximately 10-15% with increase in blood lactate levels from 4 to 10-30 mg/dl. Also, the recovery of the SvO2 in these groups following the termination of the exercise was slower in comparison to (a). The lower limit of the SvO2 level that would create oxygen debt situation in the peripheral tissues was approximately 25-30% for the exercise of 2.0 mile/h. The SvO2 reflects changes in respiratory status, pump output, hemoglobin level, and metabolism, and is thus a useful indicator to diagnose quickly the circulatory status as well as possibly to control the artificial heart output.

Animals

Mechanistic aspects of cellular interactions with artificial dialyzer membrane surfaces.

The platelet adhesion on adhesive protein-coated surfaces was significantly reduced by the addition of the synthetic tetrapeptide, RGDS (Arg-Gly-Asp-Ser), which was identified as the common amino acid sequence of adhesive site of adhesive proteins. The inhibitory effect was also observed for leukocyte(WBC) in complement-inactivated serum. No significant effect was observed for WBC in complement-activated serum. These indicate that the RGDS ligand-receptor mechanism operates on adhesive protein-adsorbed surfaces for both cellular systems and that activated complement factor (C3b)-membrane receptor (CR3) interaction operates for WBC as the complement is activated.

Amino Acid Sequence

Development and clinical application of a portable oxygen concentrator.

We have produced a compact, lightweight oxygen concentrator, using a newly-developed polymer of poly [1-(trimethylsilyl)-1-propyne] with a performance, i.e. oxygen permeability, of 61 x 10 cm3 (STP) cm/cm2 s cmHg, which is 17 times higher than that of the membrane material of conventional concentrators. The oxygen and nitrogen selectivity was 1.80. The dimensions of the apparatus are 325 x 180 x 150 mm and it weighs about 4.0 kg. It is actuated by a battery (DC 12 V, 5.6 Ah), with a 100 V AC source and a car battery (12 V) source also available. The power consumption is 70 W. The generated oxygen concentration is about 30%, and the maximum flow rate is 41/min. Applying 10 samples of various chronic pulmonary diseases to the subject, the suction of oxygen from the apparatus in the patients' rest state was conducted. An increase in the PaO2, from an average of 59.1 Torr before the suction to an average of 68.5 Torr after the suction, together with easing of breathing, was indicated. The usefulness of this apparatus for supplying portable oxygen-treatment to patients with chronic respiratory disease is shown.

Berylliosis

[Recovery of severely decompensated hearts with a left ventricular assist device].

We evaluated the limits of recovery of decompensated hearts experimentally and clinically and studied the problems of applying a left ventricular assist device (LVAD). In the chronic experiments, 16 adult goats were studied as follows: Group I consisted of seven with left ventricular infarction in a 70-80% area of the free wall induced by the multiple-ligation method; Group II, three with infarcted areas larger than 80% of the free wall; Group III, three with a 30 min anoxic arrest, and Group IV, a 45-min anoxic arrest. An LVAD was applied in all goats, and a right ventricular assist device was applied simultaneously for two goats in Group IV. Clinically, 21 patients receiving treatment with an LVAD from December 1982 to September 1988 in our center were examined. No goat in Groups II and IV could be weaned from the LVAD. Thus, the severity of artificial heart failure in Groups I and III was considered to be the limit for accomplishing restoration. In successfully-weaned cases, both in experimental and clinical settings, periods of LVAD therapy with or without IABP were less than two weeks, which was thought to be the upper time limits for LVAD application. All but one successfully-weaned patients were alive in the experiment, while clinically many patients died of multiple organ failures regardless of the results of the LVAD assistance. Analysis of data suggested that the difference was caused by the durations of the LVAD applications and weanings, the degree of right ventricular failure, the doses of catecholamine used, and the systemic care afforded, especially during tracheal intubation.

Animals

On the hemodynamics of several prosthetic heart valves: in vitro study.

Distribution of velocity, viscous shear stress and turbulence intensity in the wake of several mechanical heart valves is studied using a laser Doppler anemometer system during steady and pulsatile flow conditions. The corresponding results are also obtained for a sharp-edged orifice which help assess changes in the flow pattern caused by different valve geometries. The results are correlated with the static pressure drop across the valves and its recovery in the wake, as a function of the Reynolds number. Results suggest a substantial increase in turbulence intensity, in some cases by as much as 40- to 50-fold, thus raising a possibility of thromboembolism.

Blood Flow Velocity

Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation.

Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.

Animals