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Biomedical subjects

A Asada

Publications and source records attributed to A Asada.

At least 19 recordsLinked to original sources
PubMed1992

Minimal compartmental model of circulatory mixing of indocyanine green.

A model of indocyanine green (ICG) disposition from the moment of its injection in blood was developed. ICG disposition was characterized in five dogs deeply anesthetized with halothane, which decreased cardiac output and prolonged intravascular mixing. After ICG injection into the right atrium, femoral arterial blood samples were collected every 3 s for the 1st min and less frequently to 20 min. ICG concentrations were measured by high-performance liquid chromatography and modeled with SAAM 30.1. A fully identifiable recirculatory compartmental model with time delays was used to describe ICG disposition. The central blood volume averaged 23.4 ml/kg, and total blood volume averaged 78.9 ml/kg. Fifty-three percent of the cardiac output flowed through 14% of the peripheral blood volume while the remaining 47% flowed through 86% of the peripheral volume. This new model is isomorphic with a parallel channel, lumped-parameter circulation model and provides more information than stochastic, noncompartmental recirculatory pharmacokinetic techniques. This intravascular mixing model can be applied to determine the contribution of the circulation to drug distribution.

Analysis of Variance↗
PubMed1992

Differentiation of quail myoblasts transformed with a temperature sensitive mutant of Rous sarcoma virus. II. Relationship of myoblast fusion with calcium and temperature.

The effects of calcium and temperature on fusion of quail embryonic myoblasts were examined using cells transformed with a temperature-sensitive mutant of Rous sarcoma virus (ts-RSV). The transformed quail myoblasts (QM-RSV) fused to form myotubes at 41 degrees C, the non-permissive temperature, but not at 35.5 degrees C, the permissive temperature. On incubation at 41 degrees C, a period of more than 10 hr was needed for the myoblasts to become fusion-competent, but calcium was not needed for development of fusion-competence. Once the cells had become competent, fusion proceeded even at 35.5 degrees C. These results suggest that the src gene product expressed at 35.5 degrees C may control the fusion of cells in the competent stage by inactivating a component(s) that is associated with fusion-competence. However, fusion of even myoblasts in the competent stage was blocked in calcium-deficient medium, suggesting that calcium is essential for the fusion, probably at a step immediately before membrane union. Unlike fusion, other biochemical processes of differentiation proceeded even in calcium-deficient medium, indicating a distinction of fusion from these other processes during myoblast differentiation.

Animals↗
PubMed1991

Bone morphogenetic proteins (BMP-2 and BMP-3) promote growth and expression of the differentiated phenotype of rabbit chondrocytes and osteoblastic MC3T3-E1 cells in vitro.

We studied the effects of highly purified bone morphogenetic protein 2 and 3 (BMP-2 and -3) on growth plate chondrocytes and osteoblastic cells in vitro and compared to TGF-beta. A mixture of BMP-2 and 3 (BMPs) strongly stimulated DNA synthesis of chondrocytes in the presence of fibroblast growth factor (FGF). BMPs induced rapid maturation of chondrocytes at a growing stage: BMPs transformed the cells into rounded cells and induced marked accumulation of cartilage matrix; TGF-beta slightly reduced matrix accumulation and changed cell morphology into spindle-like in the presence of FGF. Moreover, exposure of chondrocytes to BMPs resulted in a dramatic increase of the putative approximately 80 kD PTH receptors expressed on the cell surface. In multilayered chondrocytes at the calcifying stage, BMPs stimulated alkaline phosphatase (ALPase) activity but TGF-beta inhibited it. In osteoblastic MC3T3-E1 cells, BMPs were found to be the most potent stimulator of ALPase activity thus far described: ALPase in the cells treated with approximately 100 ng/ml of BMPs reached 5- to 20-fold over the basal, whereas TGF-beta inhibited expression of ALPase activity in these cells. The stimulatory action of BMPs overrode the inhibition of ALPase activity by TGF-beta when the cells were incubated with TGF-beta and BMPs. BMPs also upregulated expression of the approximately 80 kD PTH receptor on the cells. These results suggest that BMPs have unique biologic activities in vitro that lead to growth and phenotypic expression of cells playing a critical role in endochondral bone formation.

Alkaline Phosphatase↗
PubMed1991

Effects of various growth and differentiation factors on expression of parathyroid hormone receptors on rabbit costal chondrocytes in culture.

In our preliminary report we demonstrated PTH receptors on rabbit costal chondrocytes in culture. In the present study regulation of expression of PTH receptors of the chondrocytes by various growth and differentiation factors and its relation to the synthesis of glycosaminoglycan (GAG), a differentiated phenotype of chondrocytes, were investigated. Treatment with retinoic acid decreased GAG synthesis in cultured chondrocytes and the number of PTH receptors, measured by binding of [125I]-[Nle8,18,Tyr34]bovine PTH-(1-34) amide to the cells. However, the affinity of the receptors did not change. The decrease in the number of PTH receptors was dose and time dependent and parallel to the decrease in GAG synthesis. When chondrocytes that had been treated with retinoic acid were cultured in the absence of retinoic acid for 3 days, both their GAG synthesis and their number of PTH receptors were restored. Epidermal growth factor and fibroblast growth factor also decreased both the number of PTH receptors and GAG synthesis in the cells. However, these treatments did not change their affinity. Treatment with insulin-like growth factor-I, (Bu)2cAMP, and transforming growth factor-beta resulted in increases in GAG synthesis as well as in the number of PTH receptors without any change in their affinity. In addition, the PTH-stimulated cAMP level in chondrocytes pretreated with retinoic acid, epidermal growth factor, and fibroblast growth factor was lower than that in control cells. On the other hand, the PTH-stimulated cAMP level in chondrocytes pretreated with insulin-like growth factor-I and transforming growth factor-beta was higher than that in control cells. These observations suggest that the increase in the number of PTH receptors on chondrocytes is closely related to expression of the differentiated phenotype of chondrocytes and that the number of the receptors is a good marker of the differentiated phenotype of chondrocytes.

Animals↗
PubMed1991

Treatment of atelectasis with selective bronchial suctioning. Use of a curved-tipped catheter with a guide mark.

We applied our technique of selective bronchial suctioning (SBS) for the treatment of atelectasis (AT) of middle and lower lobes; nine patients with refractory ATs were successfully treated. We considered that SBS using a curve-tipped catheter with a guide mark (CTCGM) is the technique of choice for the treatment of refractory AT when conventional respiratory therapy is not effective and a bronchoscopist is not available.

Aged↗
PubMed1990

Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage.

The growth-promoting actions of cartilage extracts (CE) on rabbit cultured chondrocytes were studied to assess the role of local acting growth factors in the generation and expansion of highly differentiated cells. In the present study, DNA synthesis and proteoglycan synthesis in the cultured chondrocytes were monitored by flow cytofluorometry and double-isotope autoradiography by using [3H]thymidine and [35S]sulfate. We report here that actions of the same set of growth factors extracted from cartilage evokes differential cellular responses depending upon cell density. Growth factors in the optimal dose of CE (2 micrograms/ml) or epidermal growth factor (EGF, 40 ng/ml) did not reveal such a cell density-dependent effect on cellular proliferation. However, growth factors in CE induced proteoglycan synthesis selectively in nonproliferating and expressing cells in confluent culture.

Animals↗
PubMed1990

Replacement of putative axial ligands of heme iron in yeast cytochrome c1 by site-directed mutagenesis.

The His-44 and Met-164 residues of yeast cytochrome c1 are evolutionally conserved and regarded as heme axial ligands bonding to the fifth and sixth coordination sites of the heme iron, which is directly involved in the electron transfer mechanism. Oligonucleotide-directed mutagenesis was used to generate mutant forms of cytochrome c1 of yeast having amino acid replacements of the putative axial ligands of the heme iron. When a cytochrome c1-deficiency yeast strain was transformed with a gene encoding the Phe-44, Tyr-44, Leu-164, or Lys-164 protein, none of these transformants could grow on the non-fermentable carbon source. These results suggest that the His-44 and Met-164 residues have a critical role in the function of cytochrome c1 in vivo, most probably as axial ligands of the heme iron. Further analysis revealed that the mutant yeast cells with the Phe-44, Tyr-44, or Leu-164 protein lacked the characteristic difference spectroscopic signal of cytochrome c1. However, in the Lys-164 mutant cells, partial recovery of the cytochrome c1 signal was observed. Moreover, the Lys-164 protein retained a low but significant level of succinate-cytochrome c reductase activity in vitro. The possibility that the nitrogen of Lys-164 served as the sixth heme ligand is discussed in comparison with cytochrome f of a photosynthetic electron-transfer complex, in which lysine has been proposed to be the sixth ligand.

Base Sequence↗
PubMed1990

Treatment of atelectasis of upper lung lobes. Selective bronchial suctioning with J-shaped catheter tip and guide mark.

We developed a technique for blind bronchial suction using a curved-tip catheter with a guide mark, for the treatment of atelectasis of the lower and middle lobes of the lung. Suction of the upper lobe bronchi could not be performed because of the combination of the peculiar anatomy of the upper lobe bronchi with catheter design. We treated successfully two cases of atelectasis of the right upper lobes using a Rusch Metras bronchography catheter with a guide mark which is not readily available. Therefore we devised a J-shape tipped catheter with a guide mark. We have successfully treated 13 episodes of atelectasis of the right upper lobe in 10 patients and one episode in the left upper lobe in one patient with this new catheter.

Bronchi↗
PubMed1990

Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s.

The metabolism of lidocaine by human hepatic microsomes and purified human cytochrome P-450s, P-450NF (P450IIIA4), P-450MP (a P450IIC form) and P-450PA (P450IA2) was examined and their metabolism was compared with that by rat hepatic cytochrome P-450s. Human hepatic microsomes produced monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-LID) from lidocaine. In a reconstituted system with dilauroylphosphatidylcholine, P-450NF efficiently produced MEGX. P-450PA was not efficient in lidocaine N-deethylation (formation of MEGX) but produced 3-OH-LID. P-450NF and P-450MP did not produce 3-OH-LID. Lidocaine N-deethylation activity of P-450NF was enhanced in a modified reconstituted system with a phospholipid mixture and sodium cholate. P-450NF appears to be an ortholog to rat P450 PB-1 (P450IIIA2). Anti-P450 PB-1 antibody cross-reacted with P-450NF and efficiently inhibited lidocaine N-deethylation in human hepatic microsomes. The correlation of lidocaine N-deethylation activity with the concentration of P-450NF determined immunochemically with anti-P450 PB-1 antibody was good (r = 0.81). In addition, correlation between P-450NF content estimated with anti-P450 PB-1 and anti-P-450NF preparations was good (r = 0.96). These results suggest that rat P450 PB-1 and human P-450NF have closely related properties and P-450NF is the major enzyme involved in lidocaine N-deethylation in human hepatic microsomes.

Adult↗
PubMed1989

Metabolism of lidocaine by purified rat liver microsomal cytochrome P-450 isozymes.

The metabolism of lidocaine was studied using rat liver microsomes or a reconstituted lidocaine monooxygenase system with one of eight forms of cytochrome P-450 purified from liver microsomes from untreated- (P450 UT-2 and UT-5), phenobarbital- (P450 PB-1, PB-2, PB-4, and PB-5) or 3-methylcholanthrene- (P450 MC-1 and MC-5) treated rats. A reverse phase high-performance liquid chromatography system capable of simultaneously assaying four major lidocaine metabolites, namely, monoethylglycinexylidide (MEGX), 3-hydroxylidocaine (3-OH LID), methylhydroxylidocaine (Me-OH LID) and glycinexylidide (GX), was employed to determine the rate of formation of each metabolite. Untreated microsomes generated MEGX, Me-OH LID, and 3-OH LID, but the formation of GX was not detected. In male rat liver microsomes, MEGX was the major metabolite of lidocaine when a concentration of 1 mM was employed. The formation of MEGX and Me-OH LID was increased significantly (P less than 0.01) by microsomes from phenobarbital-treated rats, and the formation of 3-OH LID was increased with 3-methylcholanthrene. The study with the reconstituted system with purified cytochrome P-450 isozymes revealed that all eight forms of cytochrome P-450 used have an ability to N-deethylate lidocaine to form MEGX. Among these isozymes, cytochrome P450 PB-4 and P450 UT-2 showed a higher turnover number for the formation of MEGX. Me-OH LID was formed exclusively by P450 PB-5, and 3-OH LID exclusively by P450 MC-1. Selectivity of cytochrome P450 PB-5 for aromatic methyl hydroxylation of lidocaine was confirmed by an inhibition study; formation of Me-OH LID by microsomes of rats treated with phenobarbital was inhibited completely by antibody against P450 PB-5. It was concluded that different cytochrome P-450 isozymes metabolize lidocaine with a different rate and different position selectivities. Since a specific substrate of cytochrome P450 PB-5 (P-450e) is not known, lidocaine may be a useful substrate for the identification of P450 PB-5.

Animals↗
PubMed1987

Enhanced responsiveness to parathyroid hormone and induction of functional differentiation of cultured rabbit costal chondrocytes by a pulsed electromagnetic field.

Pulsed electromagnetic fields promote healing of delayed united and ununited fractures by triggering a series of events in fibrocartilage. We examined the effects of a pulsed electromagnetic field (recurrent bursts, 15.4 Hz, of shorter pulses of an average of 2 gauss) on rabbit costal chondrocytes in culture. A pulsed electromagnetic field slightly reduced the intracellular cyclic adenosine 3',5'-monophosphate (cAMP) level in the culture. However, it significantly enhanced cAMP accumulation in response to parathyroid hormone (PTH) to 140% of that induced by PTH in its absence, while it did not affect cAMP accumulation in response to prostaglandin E1 or prostaglandin I2. The effect on cAMP accumulation in response to PTH became evident after exposure of the cultures to the pulsed electromagnetic field for 48 h, and was dependent upon the field strength. cAMP accumulation in response to PTH is followed by induction of ornithine decarboxylase, a good marker of differentiated chondrocytes, after PTH treatment for 4 h. Consistent with the enhanced cAMP accumulation, ornithine decarboxylase activity induced by PTH was also increased by the pulsed electromagnetic field to 170% of that in cells not exposed to a pulsed electromagnetic field. Furthermore, stimulation of glycosaminoglycan synthesis, a differentiated phenotype, in response to PTH was significantly enhanced by a pulsed electromagnetic field. Thus, a pulsed electromagnetic field enhanced a series of events in rabbit costal chondrocytes in response to PTH. These findings show that exposure of chondrocytes to a pulsed electromagnetic field resulted in functional differentiation of the cells.

Alprostadil↗
PubMed1984

Torsade de pointes induced by N-acetylprocainamide.

N-Acetylprocainamide (NAPA), a class III antiarrhythmic drug, caused torsade de pointes in a 72 year old woman who had this arrhythmia on two previous occasions while being treated with quinidine and disopyramide. Initial evaluation with an intravenous infusion of NAPA indicated a favorable antiarrhythmic response. The QTC interval was prolonged, but the 2.4 ms/microgram per ml incremental QTC interval lengthening caused by NAPA was not greater than usual. During subsequent oral therapy with NAPA, torsade de pointes developed at plasma levels of this drug that appeared to be well tolerated during the initial evaluation.

Acecainide↗