Biomedical subjects

S Takeoka

Publications and source records attributed to S Takeoka.

At least 37 records · Page 2Linked to original sources

PubMed1998

Human serum albumin-bound synthetic hemes as an oxygen carrier: determination of equilibrium constants for heme binding to host albumin.

Human serum albumin (HSA) incorporating synthetic tetraphenylporphinatoiron(II) derivatives (FeP1 or FeP2) can bind and release oxygen reversibly under physiological conditions (in aqueous media, pH 7.4, 37 degrees C). The maximal binding ratio of FeP1/HSA was estimated to be eight, and the stepwise equilibrium constants for FeP1 binding to HSA (K1-K8) ranged from 1.2 x 10(6) to 1.3 x 10(4) M-1. The major binding sites of FeP1 are presumably identical to those of hemin, bilirubin and long-chain fatty acids. The O2-binding ability of the HSA-FeP can be regulated by changing the molecular structure of the incorporated hemes. The half-lifetime of the O2-coordinated FeP2 in HSA was significantly longer than that of HSA-FeP1.

Binding Sites↗

PubMed1997

The oxygen carrying capability of hemoglobin vesicles evaluated in rat exchange transfusion models.

To evaluate the oxygen transporting capability of Hemoglobin vesicles (HbV) the physiological responses to 40% and 90% exchange transfusions with HbV in anesthetized rat were observed. Hb concentration of HbV dispersions is 10 g/dL. HbV dispersed in phosphate buffered saline and HbV dispersed in 5% albumin solution were used as samples for 40% and 90% exchange transfusions, respectively. HbV surface-modified with polyoxyethylene (HbV-Poe) was also used in the 90% exchange transfusion. As controls, phosphate buffered saline, 5% albumin solution, and HbV containing methemoglobin and therefore deprived of oxygen transporting capabilities (metHbV) were administered as non-oxygen carrying fluids and washed rat red blood cells (ratRBC) as an oxygen carrying fluid. Measurements included mean arterial pressure, arterial blood gas analyses, aortic blood flow and renal cortical tissue oxygen tension. At the completion of the exchange transfusion renal cortical tissue oxygen tensions along with oxygen delivery and consumption were sustained almost equally well with the HbV dispersion compared to the washed rat red blood cell dispersion, but declined significantly in the phosphate buffered saline and albumin solutions. These results indicated that the oxygen transporting capability of HbV was almost equivalent to that of rat red blood cells. In the HbV-Poe group, aortic blood flow was sustained higher in comparison to the HbV group. As for the blood gas parameters, pH and venous oxygen tensions in the HbV-Poe group tended to be higher than those in the HbV group.

Animals↗

PubMed1996

Physiologic responses to exchange transfusion with hemoglobin vesicles as an artificial oxygen carrier in anesthetized rats: changes in mean arterial pressure and renal cortical tissue oxygen tension.

OBJECTIVES: To evaluate the oxygen transporting capabilities of hemoglobin vesicles by studying the physiologic responses to exchange transfusion with hemoglobin vesicles in anesthetized rats. Exchange transfusions with phosphate buffered saline, hemoglobin vesicles containing methemoglobin (and therefore, deprived of oxygen transporting capabilities), and washed rat red blood cells were used as controls. DESIGN: Prospective, randomized, controlled trial. SETTING: Department of Surgery, School of Medicine, Keio University. SUBJECTS: Twenty-seven male Wistar rats. INTERVENTIONS: The rats were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/kg). Catheters (PE-20 tubing, outer diameter 0.8 mm, inner diameter 0.5 mm) were introduced into the right jugular vein for infusion and the right common carotid artery for blood withdrawal and mean arterial pressure measurements. The left kidney was exposed by median abdominal incision, and a needle-type polarographic oxygen electrode was placed in the left renal cortex for renal cortical tissue oxygen tension measurements. MEASUREMENTS AND MAIN RESULTS: Phosphate buffered saline and methemoglobin vesicles were administered as nonoxygen-carrying fluids, and rat red blood cells as oxygen-carrying fluid. Measurements included mean arterial pressure, arterial blood gas analysis, and renal cortical tissue oxygen tension as an indicator of systemic oxygen transport. In the rat red blood cell and hemoglobin vesicles groups, mean arterial pressure was sustained at the end of the exchange transfusion (82.3 +/- 27.5% and 73.5 +/- 11.5%, respectively, from the basal values). However, in the phosphate buffered saline and methemoglobin vesicles groups, mean arterial pressure decreased significantly (p < .05) (33.9 +/- 13.8% and 35.7 +/- 8.2%, respectively). Renal cortical tissue oxygen tension in the rat red blood cell and hemoglobin vesicles groups was sustained at a significantly higher level (p < .05) (83.5 +/- 9.3% and 75.0 +/- 11.9%, respectively) compared with the phosphate buffered saline and methemoglobin vesicles groups (44.9 +/- 12.8% and 58.3 +/- 6.2%, respectively) at the end of the exchange transfusion. Metabolic acidosis was more progressive in the phosphate buffered saline and methemoglobin vesicles groups, manifested as lower pH and base excess values. Platelet counts tended to decrease slightly in the hemoglobin vesicles and methemoglobin vesicles groups, but the changes were not significant. CONCLUSIONS: Hemoglobin vesicles have an oxygen transporting capability almost equivalent to rat red blood cells and can be considered as a potential artificial oxygen carrier.

Anesthesia↗

PubMed1995

Neutron generator at Hiroshima University for use in radiobiology study.

A neutron generator (HIRRAC) for use in radiobiology study has been constructed at the Research Institute for Radiation Biology and Medicine, Hiroshima University (RIRBM). Monoenergetic neutrons of which energy is less than 1.3 MeV are generated by the 7Li(p,n)7 Be reaction at proton energies up to 3 MeV. The protons are accelerated by a Schenkel-type-accelerator and are bombared onto the 7Li-target. An apparatus for the irradiation of biological material such as mice, cultured cells and so on, was designed and will be manufactured. Neutron and gamma-ray dose rates were measured by paired (TE-TE and C-CO2) ionization chambers. Contamination of the gamma ray was less than about 6% when using 10-microns-thick 7Li as a target. Maximum dose rates for the tissue equivalent materials was 40 cGy/min at a distance of 10 cm from the target. Energy distributions of the obtained neutrons have been measured by a 3He-gas proportional counter. The monoenergetic neutrons within an energy region from 0.1 to 1.3 MeV produced by thin 7Li or 7LiF targets had a small energy spread of about 50 keV (1 sigma width of gaussian). The energy spread of neutrons was about 10% or less at an incident proton energy of 2.3 MeV. We found that HIRRAC produces small energy spread neutrons and at sufficient dose rates for use in radiobiology studies.

Animals↗

PubMed1994

Convenient method to purify hemoglobin.

A convenient method to purify Hb solution from outdated RBC has been established for the starting material of Hb-based blood substitutes. To prevent MetHb formation during the procedure, Hb in RBC was carbonylated in advance. Then RBC was mixed with organic solvent for hemolysis and centrifuged for removal of stroma. The resulting SFHb solution was heated at 60 degrees C and generated precipitates were removed out by centrifugation. The purity of Hb (25 g/dl) was confirmed by SDS-PAGE. IEF and oxygen binding property of the Hb solution also guaranteed its purity and no denaturation of Hb. This method is applicable to large scale production of the purified Hb for the starting material of Hb-based blood substitutes.

Blood Substitutes↗

PubMed1994

Characteristics of Hb-vesicles and encapsulation procedure.

The performance of Hb-vesicles depends on the weight ratio of Hb to lipid ([Hb]/[Lipid]). This value is improved by lowering the number of bilayer membrane of the vesicle and raising the concentration of Hb in the interior of the vesicle. Maximum [Hb]/[Lipid] ratio was obtained at ca. pH 7, that would relate to the isoelectric point (pI) of Hb at 25 degrees C. On the other hand, the [Hb]/[Lipid] ratio decreased with ionic strength and increased with lowering temperature. The Hb-vesicles encapsulating 40 g/dl Hb with only one bilayer membrane were isolated by using the difference in the density of the vesicles.

Blood Substitutes↗

PubMed1993

Purification of concentrated hemoglobin using organic solvent and heat treatment.

A simple method for obtaining a purified and concentrated hemoglobin (Hb) solution (25 g/100 ml) from human red blood cells has been established. To prevent MetHb formation during the purification procedure, Hb in red blood cells was carbonylated in advance, and then washed red blood cells were mixed with organic solvents such as diethyl ether or dichloromethane for hemolysis and removal of stroma. The Hb solution was isolated by centrifugation (1900g) with the high removal efficiency of phospholipid (> 99.8%). After the solution was heated (60 degrees C, 1 h), the precipitates were removed by centrifugation. The purity of Hb was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isoelectric focusing and oxygen-binding properties of the obtained Hb solution demonstrated its purity and showed no denaturation of globin. This purification procedure is applicable to large-scale production of the purified Hb.

Calorimetry↗

PubMed1993

Dose-rate effects of neutrons and gamma-rays on the induction of mutation and oncogenic transformation in plateau-phase mouse m5S cells.

The dose-rate effect of 252-californium neutrons was investigated using confluent cultures of mouse m5S cells. The relative biological effectiveness (RBE) of neutrons for oncogenic transformation was increased from 3.3 to 5.1 when the dose-rate was reduced from 1.8 to 0.12 cGy/min. Similarly, neutron RBE values for HPRT- mutation were 4.9 and 7.4 at dose-rates of 1.8 and 0.12 cGy/min, respectively. The increases in RBE as dose-rate was reduced were due mainly to diminished transformation- and mutation-induction by gamma-rays (the standard radiation). The yields of neutron-induced oncogenic transformation as well as neutron-induced mutation were constant for both dose rates. Our observation contrasts with reports by others using proliferating cells where both oncogenic transformation and mutation were enhanced with neutron exposure at a reduced dose-rate, the so-called inverse dose-rate effect. Since m5S cells are sensitive to postconfluent inhibition of cell division, this observation could be ascribed to cell growth conditions used in these experiments. The mechanism of the inverse dose-rate effect of neutrons suggests that the enhancement of neutron-induced mutation and oncogenic transformation at a reduced dose-rate is strongly associated with cell proliferation during exposure.

Animals↗

PubMed1992

Oxygen-transport and solution properties of polylipid/Hb vesicles (ARC).

Polymerized phospholipid vesicle encapsulating Hb (polylipid/Hb vesicle) was prepared from a mixture of unsaturated phospholipid, cholesterol and unsaturated fatty acid and polymerization by gamma-ray irradiation. The average radius of resulting vesicles was 203 +/- 39 nm and concentrated Hb (30 wt%) was efficiently encapsulated. gamma-Ray polymerization proceeds theoretically at low temperature (4 degrees C). P50 and oxygen transporting efficiency were adjusted to 40 mmHg and 40%, respectively. Oncotic pressure and solution viscosity can be controlled to the same values as blood.

Blood Substitutes↗

PubMed1988