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Biomedical subjects

J Ando

Publications and source records attributed to J Ando.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and antitumor activity of tropolone derivatives. 7. Bistropolones containing connecting methylene chains.

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.

Animals↗
PubMed1992

The effects of two EFL (English as a foreign language) teaching approaches studied by the cotwin control method: a comparative study of the communicative and the grammatical approaches.

The present study compared two different types of English-language teaching approaches, the grammatical approach (GA) and the communicative approach (CA), by the cotwin control method. This study has two purposes: to study the effects of teaching approaches and to estimate genetic influences upon learning aptitudes. Seven pairs of identical twins (MZ) and 4 pairs of fraternal twins (DZ) participated in the experiment along with 68 other nontwin fifth graders. Each cotwin was assigned to the GA and CA respectively and received 20 hours of lessons over a 10-day period. The behavioral similarities between MZ cotwins were statistically and descriptively depicted. No major effect of either teaching approach was noted, but the genetic influence upon individual differences of learning achievement was obvious. Furthermore, an interesting interaction between the teaching approaches and intelligence was found, that is, that the GA capitalises on and CA compensates for intelligence. This interactional pattern could be interpreted as an example of genotype-environment interaction. The relationship between genetic factors and learning aptitudes is discussed.

Aptitude Tests↗
PubMed1991

Effect of extracellular ATP level on flow-induced Ca++ response in cultured vascular endothelial cells.

Cultured vascular endothelial cells loaded with the highly fluorescent Ca(++)-sensitive dye Fura-2 were exposed to the flow of a fluid containing various concentrations of ATP (0, 0.5, 1, 5 microM) in an apparatus designed on the basis of fluid dynamics, and simultaneous changes in intracellular free Ca++ concentration were monitored by photometric fluorescence microscopy. The flow rate of the perfusate was altered from 0 to 6.3 to 22.8 to 39.0 cm/sec, inducing shear stress on the cell surface of 0, 2.9, 10.4, and 17.9 dynes/cm2, respectively. Although no significant change in intracellular Ca++ level was observed at ATP levels below 100 nM, at an ATP level of 500 nM, the intracellular Ca++ level increased together with an increase in the flow rate of the perfusate. At this level of ATP, the intracellular Ca++ levels at flow rates of 0, 6.3, 22.8, and 39.0 cm/sec were 44.8 +/- 7.3, 60.3 +/- 10.7, 74.0 +/- 5.8 and 89.4 +/- 6.4 nM (mean +/- SD; n = 8), respectively. At ATP levels over 1 microM, the flow-rate dependency of Ca++ response became less clear than that observed at the ATP level of 500 nM. These Ca++ responses to changes in flow rate disappeared when extracellular Ca++ was chelated by adding 2 mM of EGTA to the perfusate. These results suggest that the vascular endothelial cell has a mechanism that elevates the intracellular Ca++ level in accord with the flow rate at appropriate ATP concentrations, and that changes in intracellular Ca++ level under this mechanism seem to be chiefly caused by the influx of extracellular Ca++ into cells.

Adenosine Triphosphate↗
PubMed1991

Culture of human adult endothelial cells on liquid-liquid interfaces: a new approach to the study of cell-matrix interactions.

Human adult endothelial cells (ECs) were cultured on liquid-liquid interface formed when aqueous culture medium is overlaid onto a fluorocarbon solvent. When ECs were seeded on untreated interfaces, some cells seemed to attach but they did not spread or grow. In contrast, when ECs were seeded on interfaces pretreated with such proteins as collagen type IV (COL), laminin (LN), fibronectin (FN), and fibrinogen (FG) the cells spread and proliferated until they formed confluent monolayers. Proteins such as bovine serum albumin (BSA) or gelatin (GN) were not as effective in providing surfaces for vigorous growth. Cells grown on fluorocarbon interfaces expressed specialized characteristics exhibited by endothelial cells grown under the usual culture conditions; they grew in a cobblestone monolayer, stained positively for Factor VIII-related antigen, and produced angiotensin-converting enzyme. The growth rate of ECs was the same whether they were cultured on treated fluorocarbon interfaces or on the usual tissue culture plastic surfaces. Using this culture system, the interactions of ECs with various adhesive proteins used as substrata was examined. ECs were observed to attach readily to the interfaces coated with GN, COL, LN, FN, and FG, but poorly to those coated with BSA. All the substrates tested, with the exception of BSA, promoted EC growth on fluorocarbon interfaces; ECs tended to grow more rapidly on COL- or FG-coated interfaces than on LN-, FN-, or GN-coated interfaces.

Animals↗
PubMed1991

Flow effects on cultured vascular endothelial and smooth muscle cell functions.

Cultured vascular endothelial cells were exposed to fluid shear stress by means of a rotary-disc shear-loading device, and the physiological effects of the conditioned medium (CM) and the homogenate (HM) of the cells on migration, adhesion and growth of endothelial cells (EC) or smooth muscle cells (SMC) were studied. Effects of shear stress on the production and secretion of collagen, one of the extracellular matrices of EC, were also studied. CM stimulated the adhesion and growth of SMC, but not of EC themselves. The ability to stimulate SMC adhesion and growth was similar in CM obtained from the static and shear-loaded cells. HM of the shear-loaded EC stimulated SMC migration. Further, HM of the shear-loaded EC contained increased amounts of collagen compared with the static EC. These results suggest that: 1) EC produce and secrete accelerators for the adhesion and growth of SMC, 2) EC react to the physical stimulus of fluid shear stress to produce stimulators of SMC migration, and 3) EC produce collagen, the production of which is enhanced by fluid shear stress.

Animals↗
PubMed1991

Pressure-volume relationships of finger arteries in healthy subjects and patients with coronary atherosclerosis measured non-invasively by photoelectric plethysmography.

Knowledge of the mechanical properties of the small arteries is important for understanding physiological and pathophysiological conditions in the human peripheral circulation. We have recently developed a new method for the noninvasive measurement of arterial elastic properties in human fingers using photoelectric plethysmography. In this study, the pressure-volume relationship, an index for expressing arterial elasticity, was measured by this method in the finger arteries of 91 healthy subjects and 102 patients with coronary artery disease. Aging effects on the elastic properties of finger arteries were examined in healthy subjects classified into three groups: under 30, 31-49, and over 50 years of age. The pressure-volume curve shifted downward with increase in age, indicating that the elasticity of finger arteries decreased with age. Patients with 75% or greater coronary stenosis, as compared with age-matched healthy subjects, showed distinctly lower elasticity of finger arteries. As the number of diseased coronary arteries increased, the elasticity of finger arteries tended to decrease steadily. The elasticity of finger arteries decreased in coronary disease patients with hypertension much more than in those without hypertension. These results suggest that age-related changes in arterial elasticity can occur in peripheral small arteries, and that peripheral arteries in patients with coronary atherosclerosis are less elastic than those in healthy subjects.

Adult↗
PubMed1990

The efficiency of the vascular-tissue system for oxygen transport in the skeletal muscles.

The efficiency of the vascular-tissue system for oxygen (O2) transport in the skeletal muscle was estimated by using Krogh's cylinder model for the capillary-tissue arrangement. The tissue mass supplied by a single capillary was calculated as the region of positive O2 tension. For given values of total muscle flow and tissue O2 consumption rate, total tissue mass was determined as the function of the capillary number (n). The energy cost to maintain the vascular system with n terminals (capillaries) was assessed by the minimum volume model by Kamiya and Togawa (1972). The efficiency of the entire system was evaluated by calculating the ratio of (total tissue mass) or (total O2 consumption)/(the energy cost). The results of the calculation using physiological data of muscle blood flow and O2 consumption rate in man during exercise revealed the optimum capillary number to be around 1.5 x 10(10) and the Krogh cylinder radius to be 26 microns, which agrees well with the morphological data of these values in human skeletal muscles. It was concluded that the vascular-tissue system in the skeletal muscle is constructed so as to attain the highest efficiency in O2 transport to tissue during exercise.

Animals↗
PubMed1990

Effects of preparing and ligand-binding methods of small unilamellar liposomes on their blood elimination and tissue distribution in rats.

The effects of two methods of preparing small unilamellar vesicles (SUV) (detergent removal or sonication) on their in vivo elimination and tissue distribution was investigated in rats. The SUV prepared by either method had the same size distribution and lipid composition (egg yolk phosphatidylcholine/cholesterol/dipalmitoyl phosphatidylethanolamine or palmitic acid = 20/10/0.3, molar ratio). Three types of SUV made by either method were prepared. These contained one of three different surface ligand-binding functional groups (N-hydroxysuccinimide ester of palmitic acid, NHSP; glutaraldehyde-phosphatidylethanolamine, GA-PE; N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine, MPB-PE). SUV prepared by detergent removal were eliminated slowly from the circulation, and exhibited a low liver uptake and little leakage of [3H]inulin. There was no significant difference in elimination of the NHSP-SUV, GA-SUV or MPB-SUV prepared by detergent removal and their tissue distribution was similar. In contrast, the sonicated SUV were eliminated from the circulation much more rapidly mainly by liver uptake. The leakage of [3H]inulin from sonicated SUV into urine was relatively large. When sonicated control-SUV were prepared in the presence of the antioxidant, alpha-tocopherol (alpha-T-SUV), which reduces lipid peroxidation during sonication, the alpha-T-SUV were eliminated slowly with only a low liver uptake. Our results indicate that the rapid elimination and greater liver uptake of sonicated SUV is partly due to lipid peroxidation during preparation. These findings have relevance to the use of liposomes as a drug delivery system.

Animals↗
PubMed1990

Fluid shear stress enhanced DNA synthesis in cultured endothelial cells during repair of mechanical denudation.

We have previously observed a stimulatory effect of fluid shear stress on the regeneration of cultured endothelial cell layers after mechanical denudation. In this study we examined how fluid shear stress affects endothelial cell DNA synthesis during regeneration. Following mechanical denudation of narrow linear areas, monolayers of bovine aortic endothelial cells cultured on plastic dishes were subjected to shear stress of 1.3-4.1 dynes/cm2 for 24-48 hours in a specially designed apparatus. After the application of shear stress, cells were stained with propidium iodide, and its fluorescence intensity, reflecting cellular DNA content, was measured using photometric fluorescence microscopy. The DNA content of cells exposed to shear stress increased significantly more than that of paired, static control cells (p less than 0.005 to p less than 0.001). The DNA histogram showed that cells exposed to shear stress contained a relatively high proportion of cells located in the S, G2, and M phases of the cell cycle as compared with the static control. These data suggest that fluid shear stress enhances endothelial cell DNA synthesis during the repair of mechanical denudation.

Animals↗
PubMed1990

[Fluid shear stress effects on intracellular calcium concentrations in cultured vascular endothelial cells].

Vascular endothelial cells are known to modulate their functions in response not only to humoral stimuli but also to such physical stimuli as fluid shear stress generated by blood flow. However, the mechanisms by which the hemodynamic force acts on endothelial cells are not yet well understood. We have studied how endothelial cells recognize the shear stress and mediate it to intracellular organelles. Cultured monolayers of bovine aortic endothelial cells loaded with the highly fluorescent Ca+(+)-sensitive dye Fura 2 were exposed to different levels of fluid shear stress in a specially designed flow chamber and simultaneous changes in intracellular-free Ca+(+) concentration were measured using photometric fluorescence microscopy. Application of shear stress to cells by fluid perfusion led to an immediate several-fold increase in Ca+(+) concentration within 1 min, followed by a rapid decline, and finally a plateau somewhat higher than control levels during the entire period of the stress application. The early part of the response, but no plateau, was observed even in Ca+(+)-free medium added with 2 mM EDTA, and in the presence of calcium antagonists (e.g. 2 x 10(-5) M nicardipine). Thus, endothelial cells may have a flow-sensing property which recognize the shear stress on the membrane as a stimulus and mediates the signal to increase intracellular free Ca(+)+ which is a major component of the internal signalling system of the cell.

Animals↗
PubMed1988

Cytoplasmic calcium response to fluid shear stress in cultured vascular endothelial cells.

Vascular endothelial cells modulate their structure and functions in response to changes in hemodynamic forces such as fluid shear stress. We have studied how endothelial cells perceive the shearing force generated by blood flow and the substance(s) that may mediate such a response. We identify cytoplasmic-free calcium ion (Ca++), a major component of an internal signaling system, as a mediator of the cellular response to fluid shear stress. Cultured monolayers of bovine aortic endothelial cells loaded with the highly fluorescent Ca++-sensitive dye Fura 2 were exposed to different levels of fluid shear stress in a specially designed flow chamber, and simultaneous changes in fluorescence intensity, reflecting the intracellular-free calcium concentration [( Ca++]i), were monitored by photometric fluorescence microscopy. Application of shear stress to cells by fluid perfusion led to an immediate severalfold increase in fluorescence within 1 min, followed by a rapid decline for about 5 min, and finally a plateau somewhat higher than control levels during the entire period of the stress application. Repeated application of the stress induced similar peak and plateau levels of [Ca++]i but at reduced magnitudes of response. These responses were observed even in Ca++-free medium. Thus, a shear stress transducer might exist in endothelial cells, which perceives the shearing force on the membrane as a stimulus and mediates the signal to increase cytosolic free Ca++.

Animals↗
PubMed1988

Sex differences in [3H]nitrendipine binding and effects of sex steroid hormones in rat cardiac and cerebral membranes.

The sex differences and regulation by sex steroid hormones in calcium channels were studied by using [3H]nitrendipine binding to cardiac and cerebral membranes in 15-week old spontaneously hypertensive rats (SHRs). The maximal number of binding sites (Bmax) in the hippocampus of female SHRs increased by 24.1% over that in male SHRs. In the females, the Bmax values in the cardiac, striatal, thalamic and hippocampal membranes from ovariectomized SHRs decreased by 34.7, 29.9, 29.3 and 26.9%, respectively, compared to normal SHRs. This phenomenon, except for the hippocampus, was inhibited by estradiol but not by testosterone. In the male, the Bmax values in cardiac and cerebral membranes showed almost no changes after orchidectomy or treatment with estradiol or testosterone. After gonadectomy, the Bmax values in the cardiac, striatal and thalamic membranes of females decreased by 30.2, 33.0 and 35.6%, respectively, compared to those in males. The changes in apparent dissociation constant (KD) values were less remarkable than those in the Bmax values. These findings suggest that sex differences exist in the calcium channels of the heart, striatum, thalamus and hippocampus, and they suggest that estradiol, but not testosterone, may play a part in the regulation of the calcium channels in female SHRs.

Animals↗
PubMed1988

Roles of fluid shear stress in physiological regulation of vascular structure and function.

The effects of fluid shear stress on the function and structure of the vascular system are outlined, based on the findings obtained in our laboratory or of our colleagues. First, it is pointed out that the adaptive response of the vascular wall to flow changes which we observed in the canine carotid artery shunted with the jugular vein altering the internal diameter to keep the wall shear stress constant, can attain the optimum vascular branching structure as predicted in the minimum work model by Murray. Electronmicroscopic studies of similarly shunted arteries revealing various morphological changes in the endothelial cells have suggested that the shear stress initially affects the endothelium. The in vitro experiments using cultured endothelial cells as well have exhibited that the mitotic activity of the cells significantly increases by applying fluid shear stress. From these findings, it is concluded that the adaptive response of the endothelium to the fluid shear stress is an inherent and key process locally regulating the vascular system to be in the most functional state.

Animals↗
PubMed1988

A disk-type apparatus for applying fluid shear stress on cultured endothelial cell.

To study the effect of fluid shear stress on cultured endothelial cells, we have developed an apparatus for the stress creation, which consists of a stainless steel disk driven by an electric DC motor and a stage to place a culture dish and to adjust the distance between the disk and the dish. When the disk is rotated, a concentric fluid movement occurs in the culture medium in the dish and exerts the shear stress on the endothelial cells cultured on the bottom of the dish. A theoretical analyses concerning the induced concentric flow velocity predicted that when the angular velocity of the disk rotation (omega) is slow enough to maintain a Reynolds' number of the order of 10, the exerted wall shear stress tau w on the endothelial cell monolayer is given for a constant as tau w = mu r omega/d where mu is the viscosity of the medium, d the distance from the plate to the monolayer and r the radial distance from the center of the dish. When omega is varied in a sinusoidal mode tau w also becomes sinusoidal, thus allowing to apply a pulsatile stress. In vitro experiments carried out to examine the validity of the theoretical results, using a suspension of polystyrene as a tracer with the ordinary culture medium and 99% ethanol, revealed excellent agreement of the measured velocity profiles with the predicted ones. The results demonstrated that the present apparatus can create both the steady and pulsatile wall shear stress on the culture cell layer as expected, unless Reynolds' number greatly exceeds the level of 10.

Cells, Cultured↗
PubMed1987

The effect of fluid shear stress on the migration and proliferation of cultured endothelial cells.

We have examined the effect of shear stress on the regenerative response of cultured vascular endothelial cells by using a fluid shear apparatus designed in our laboratory. The shear stress was created on the endothelial cell layer of a fetal calf and grown confluently in a culture dish by whirling the medium, with a rotating disk placed on the fluid surface. The effect of the shear load (0.3-1.7 dyn/cm2) over 24 hr was evaluated by counting the number of regenerated cells in a denuded area that had been created by mechanically removing some cells before rotating the medium. The cell number observed in the denuded area after the exposure to shear stress was about twice as great as that of the static control. The difference was statistically significant (P less than 0.01 to P less than 0.05). Cell migration and proliferation occurred more prominently in the downstream portion of the flow than in the upstream part. The cell number in the downstream portions correlated significantly with the intensity of the applied shear stress (P less than 0.05). These results indicate that shear stress can stimulate the migration and proliferation of endothelial cells.

Animals↗
PubMed1986

Binding of [3H]nitrendipine to cardiac and cerebral membranes from normotensive and renal, deoxycorticosterone/NaCl and spontaneously hypertensive rats.

The properties of [3H]nitrendipine binding to cardiac and cerebral membranes from normotensive Wistar-Kyoto (WKY) and renal (RHR), deoxycorticosterone/NaCl (DOCA-HR) and spontaneously hypertensive (SHR) rats were investigated. The maximal numbers of binding sites (Bmax) in the striatum, thalamus and hippocampus for SHR increased by 21.4-40.0, 28.1-40.4 and 21.4-34.1% of the numbers in WKY, but the apparent dissociation constants (KD) in the cerebral membranes differed very little between WKY and SHR. In the cardiac membranes, KD and Bmax values differed very little between WKY and SHR. In the RHR and DOCA-HR, the Bmax values in the striatum, thalamus and hippocampus were similar to those of WKY. These findings suggest that the increase in Bmax of [3H]nitrendipine in the striatum, thalamus and hippocampus of SHR may play a part in the development and maintenance of high blood pressure in SHR.

Animals↗