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Biomedical subjects

J Ando

Publications and source records attributed to J Ando.

At least 73 records · Page 4Linked to original sources
PubMed1996

Blood gas profiles of fetuses with abnormal Doppler flow in the umbilical artery.

This study was designed to show how accurately the pulsed Doppler fetal blood flow velocimetry reflects fetal blood gas values. Abnormal Doppler umbilical artery (UA) velocimetry was defined when the value deviated from the 95% confidence interval of the normal fetuses. Fetal acidemia, hypoxemia, or hypercapnia was defined when the fetal blood gas taken by funipuncture during pregnancy deviated from the 95% confidence interval of the standard. Positive predictive values of abnormal UA Doppler with acidemia, hypoxemia, and hypercapnia were 26.3, 29.2, and 25.4%, respectively. When an absence or reversal of diastolic flow was observed, positive predictive values of absence or reversal of UA Doppler were 71.4 for acidemia, 71.4 for hypercapnia, and 71.4 for hypoxemia. In conclusion, although it is difficult to presume the fetal blood gas profile by Doppler velocimetry alone, we have to recognize the deterioration of the fetal blood gas profile when we observe the absence or reversal in diastolic flow in the UA.

Blood Flow Velocity↗
PubMed1996

Flow-dependent regulation of gene expression in vascular endothelial cells.

Vascular endothelial cells are constantly exposed to wall shear stress generated by blood flow. Endothelial cells act as mechanoceptors sensing and responding to shear stress, and play a role in flow-dependent phenomena such as angiogenesis, vascular remodeling and atherosclerosis. Numerous recent studies have demonstrated that endothelial cell functions change in response to shear stress, and that the responses are often accompanied by changes in related gene expression. More recently there has been evidence that genes known to be regulated by shear stress may have a common cis-element (shear stress responsive element; SSRE) in their promoter regions. A molecular mechanism for endothelial cell responses to mechanical stress is close to being elucidated. In this paper, shear-stress-mediated regulation of endothelial gene expression is reviewed.

Blood Circulation↗
PubMed1996

[Shear stress and vascular formation].

Blood flow plays important roles in the morphogenesis of blood vessels. For instance, increases in blood flow induce dilatation of the blood vessels, while decreases in blood flow cause reduction of vessel diameter. Blood flow also stimulates angiogenesis. In these blood flow-dependent phenomena, wall shear stress generated by flowing blood that acts on vascular endothelial cells works as a key factor. Numerous in vivo and in vitro studies have demonstrated that mechanical forces, shear stress, actually modulate the morphology and many functions of endothelial cells, and these forces also alter their gene expression. More recently, a cis-acting shear stress responsive element was identified in the promoters of endothelial genes that respond to shear stress, suggesting a common mechanism linking biomechanical forces to gene expression. Details of the process in which shear stress-mediated changes in endothelial cell functions lead to vascular remodeling and angiogenesis, however, are not entirely clear. Elucidation of this problem will give us not only a better understanding of the morphogenesis of blood vessels but also new therapies that can help manage or prevent cardiovascular diseases including atherosclerosis.

Biomechanical Phenomena↗
PubMed1995

Flow stimulates ICAM-1 expression time and shear stress dependently in cultured human endothelial cells.

Human umbilical vein endothelial cells were subjected to controlled levels of shear stress in a flow-loading apparatus, and changes in the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were measured by flow cytometry. Application of shear stress (15 dynes/cm2) increased the cell surface expression of ICAM-1 2.7 times the control level 4 hr after the onset of flow, while it caused no change in VCAM-1 expression. The increase of ICAM-1 expression by shear stress was time- and force-dependent and reversible. Flow loading using perfusates with different viscosity revealed that the increase in ICAM-1 was shear-stress- rather than shear-rate-dependent. Reverse transcriptase/polymerase chain reaction analysis showed upregulation of ICAM-1 mRNA levels by shear stress, whose time course closely paralleled that of the cell surface protein. These results suggest that shear stress generated by blood flow acts as a regulator of cell adhesion molecule expression on vascular endothelial cells.

Base Sequence↗
PubMed1995

Down-regulation of vascular adhesion molecule-1 by fluid shear stress in cultured mouse endothelial cells.

This study was undertaken to determine whether blood flow modulates the adhesive property of vascular endothelial cells to lymphocytes and, if it does, what adhesion molecules are involved. Cultured mouse endothelial cells were exposed to medium flow in a parallel plate chamber, and binding assay using fluorescence-labeled lymphocytes was carried out. The adhesion rate of endothelial cells to lymphocytes, which was high in the static control state, decreased when exposed to shear stress (1.5 dynes/cm2) for 6 h. The treatment of static endothelial cells with a monoclonal antibody of vascular cell adhesion molecule-1 (VCAM-1) depressed the adhesion rate to the same extent as that caused by flow, while monoclonal antibodies of CD44 and intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis revealed that the application of flow decreased markedly the amount of VCAM-1 expressed on the cell surface. A reverse transcriptase-polymerase chain reaction of mRNA showed that flow depressed VCAM-1 mRNA levels. These results suggest that blood flow can modulate the adhesive property of endothelial cells to lymphocytes via affecting the surface expression of adhesion molecules, e.g., down-regulation of VCAM-1.

Animals↗
PubMed1995

[Immunoglobulin and LST in RA patients treated with bucillamine].

In 79 RA patients treated with Bucillamine (Bu) we monitored IgG, A, M and total protein concentration x gamma-globulin% (Ig) before and after Bu. All of these four were lowered after Bu in both groups with and without adverse reaction. In the group with adverse reactions the serum level of IgG, A and Ig was significantly lower after Bu treatment than in the group without adverse reactions. The decreases of IgG and IgA were statistically significantly greater in the group with adverse reactions than those in the group without adverse reaction. The serum level of IgM after Bu in the effective group was significantly lower than that in the non-effective group. We also examined lymphocyte stimulation test (LST) in 44 RA patients treated with Bu. In the effective group Bu inhibited lymphocyte proliferative response to PPD more significantly than in the non-effective group. Bu also inhibited lymphocyte proliferative response after stimulation with PPD in the non-effective group doseresponsively. We concluded that the considerable decreases of IgG and IgA might correlate with the adverse reactions of Bu. The decrease of IgM and inhibition of LST with Bu might correlate with the efficacy of Bu.

Aged↗
PubMed1994

Fluid shear stress increases the expression of thrombomodulin by cultured human endothelial cells.

Endothelial cells (ECs) cultured from human umbilical vein were exposed to medium flow in a flow-loading chamber, and changes in thrombomodulin (TM) expression were examined by flow cytometry and enzyme linked immunosorbent assay with monoclonal antibody. The expression of TM antigen was increased time- and shear stress-dependently by flow, and when exposed to a shear stress of 15 dynes/cm2 for 24 hr, it increased to approximately 200% of the stationary control level. Reverse transcriptase-polymerase chain reaction showed that TM mRNA levels in ECs also increased in response to flow. TM mRNA began to increase one hour after the application of shear stress of 15 dynes/cm2 and reached a maximum (approximately 330% of stationary control) after eight hours. These results, demonstrating an up-regulating effect of flow on TM expression in ECs, suggest that shear stress may be an important modulator of intravascular blood coagulation.

Antibodies, Monoclonal↗
PubMed1994

Exogenous nitric oxide inhibits proliferation of cultured vascular endothelial cells.

Cultured bovine fatal aortic endothelial cells (BAECs) were stimulated with nitric oxide (NO)-releasing vasodilators and NO gas-saturated solution, and changes in the cell proliferation were examined. Sodium nitroprusside (SNP) and nitroglycerin (NTG) shifted the growth curve downward, and inhibited 3H-thymidine incorporation by the ECs in a dose-dependent manner. Application of NO solution also reduced 3H-thymidine incorporation. SNP, NTG and NO solution increased the intracellular cGMP in BAECs. A cGMP analog, 8-bromo-cGMP, inhibited 3H-thymidine incorporation, and a guanylate cyclase inhibitor, methylene blue, almost completely blocked the inhibitory effect of SNP and NTG on 3H-thymidine incorporation. These findings suggest that exogenous NO inhibits EC proliferation, and that intracellular cGMP is involved in the inhibitory effect of NO.

Animals↗
PubMed1994

Laminar flow stimulates ATP- and shear stress-dependent nitric oxide production in cultured bovine endothelial cells.

Based on the fact that nitric oxide (NO) production is associated with changes in intracellular cGMP levels and is selectively inhibited by N omega-methyl L-arginine (L-NME), we investigated the shear stress dependency of NO production in endothelial cells (ECs) from its cGMP responses to various shear stress loads. Cultured fetal bovine aortic ECs treated with a phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX; 1 mM), were exposed to a laminar flow of Krebs buffer solution for 5 minutes in a parallel-plate flow chamber and examined for changes in intracellular cGMP levels by radioimmunoassay using an [125I] cGMP kit. Application of flow increased the cGMP levels. The increase was significant in the presence of extracellular ATP (1 microM)(control, 286.1 +/- 43.6; flow, 506.5 +/- 44.9 fmol/10(7) cells; p < 0.001), but not in its absence (control, 256.6 +/- 60.6; flow, 301.5 +/- 91.4 fmol/10(7) cells; N.S.). The cGMP levels increased significantly as the magnitude of shear stress applied increased. Treatment of ECs with a specific inhibitor of NO production, L-NMA (200 microM), completely inhibited the flow-induced increase in cGMP, and L-arginine reversed the L-NMA-induced inhibition, indicating that the increase in cGMP was due to NO produced by the flow. The flow-induced increase in NO production was markedly suppressed when extracellular Ca++ was chelated by adding EGTA to the perfusate. These findings suggest that flow stimulates NO production to increase cGMP levels shear stress-dependently in ECs and that extracellular Ca++ and ATP modulate the effects of flow.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression.

Monolayers of endothelial cells (EC) cultured from mouse lymph nodes were exposed to controlled levels of shear stress (0-7.1 dyn/cm2) in a parallel plate flow chamber, and binding between the flow-loaded EC and mouse lymph node-derived lymphocytes was assayed. A large number of lymphocytes adhered to the stationary control EC, but in EC exposed to a shear stress of 1.5 dyn/cm2 for 6 h, the adhesion decreased to 68.8 +/- 12.8% (SD; n = 19) of control (n = 29, P < 0.001). The decrease in adhesion induced by flow loading was time and shear stress dependent and reversible. Treatment of stationary EC with a monoclonal antibody (MAb) to vascular cell adhesion molecule-1 (VCAM-1) reduced the adhesion to 70.6 +/- 11.5% (n = 19) of control (P < 0.001), whereas MAb to CD44 and to intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis revealed that the amount of VCAM-1 expressed on the cell surface was decreased to 48.5 +/- 15.8% (n = 6) of control by flow loading (P < 0.001). Flow loading experiments using two perfusates with different viscosities demonstrated that the decrease in VCAM-1 expression due to flow was shear stress rather than shear rate dependent. The detection of mRNA by reverse transcriptase-polymerase chain reaction showed that VCAM-1 mRNA levels were markedly depressed in EC exposed to flow loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Treatment of advanced colorectal cancer with long-term continuous infusion of 5-fluorouracil].

The purpose of the study was to evaluate the efficacy of long-term continuous administration of 5-fluorouracil (5-FU) in ambulatory patients with colorectal cancer. Nineteen patients with advanced colorectal cancer were treated with continuous intravenous infusion of 5-FU (500 mg/day). The minimum duration of therapy was projected to be four weeks. In some patients 4 weeks interval therapy was selected and in other patients the duration of therapy was open-ended. A portable pump was used to deliver 5-FU continuously into the venous system at home. The pump had a subcutaneously placed port connected to a central venous catheter. In 19 patients, the duration of 5-FU infusion was 56 to 427 days (median: 139 days), and cumulative doses of 5-FU ranged from 28 to 173.5 g (median 69.5 g). Five patients achieved partial response (response rate: 26.3%), and the response lasted 80 to 339 days (median: 204 days). The fifty-percent survival time was 17 months. In 16 patients whose serum CEA level was elevated, there was a decrease to less than 50% among 11 patients (69%). Dose limiting toxicity was stomatitis in 4 patients and hand-foot syndrome in one, but they recovered after interruption of the infusion. Hematological toxicity was generally mild. No infusion-system related complication was encountered. Patients were able to be discharged and live at home during 82% of their survival period, while receiving this therapy. We concluded that this treatment is effective with tolerable toxicity and can be conducted at home.

Aged↗
PubMed1994

[Phase I study of CGS16949A--a new aromatase inhibitor. Cooperative Study Group for CGS16949A].

Phase I study of CGS16949A--a new aromatase inhibitor--was performed in postmenopausal women with advanced breast cancer who received either single oral administration of 4 and 8 mg, or multiple oral daily administration of 1, 2, 4, 8 and 16 mg for 5.5 days. No side effects were observed after single dose administration of 4 mg and 8 mg of CGS16949A. In the multiple administration, one patient received 1 mg/day for 3 days complained of abdominal pain (Grade 2), but administration of CGS16949 A was continued despite of the pain. In order to assess the causal relationship of the drug with the abdominal pain, the number of patients in 1 mg/day group was doubled from 3 to 6 patients, but no side effects were observed in the remaining five patients. In addition, no side effects, including abdominal pain, were noted in the other 2, 4, 8 and 16 mg/day groups. After multiple administration, plasma concentrations of estradiol at 5 hrs after the final dosage in the respective dose groups were reduced to 47.1 +/- 8.3%, 37.3 +/- 3.0%, 28.0 +/- 7.8%, 26.0 +/- 11.3% and 26.6 +/- 13.8% respectively. Similar tendencies were observed in estrone plasma levels and urinary estrogens levels. In this study, the reduction of plasma estrogen levels was confirmed following administration of CGS 16949A. The clinical usefulness of this new aromatase inhibitor remains to be studied further.

Administration, Oral↗
PubMed1993

The effect of flow on the expression of vascular adhesion molecule-1 by cultured mouse endothelial cells.

Adherence of leukocytes to vascular endothelial cells (ECs) is known to be sensitive both to blood flow and adhesive proteins on EC surface. To elucidate the effect of blood flow on the surface expression of adhesive proteins, cultured ECs derived from mouse lymph nodes were exposed to different levels of wall shear stress in a flow-loading chamber, and changes in the expression of vascular adhesion molecule-1 (VCAM-1) and CD44 were evaluated by immunostaining with monoclonal antibodies and flow cytometry. Both proteins were expressed on non-activated cultured ECs. When exposed to flow with shear stress of 1.5 dynes/cm2 for 24 hr, VCAM-1 nearly disappeared on fluorescence micrographs, while CD44 showed no change. Flow cytometric analysis showed that the mean channel fluorescence of VCAM-1 was decreased about 75% by application of flow for 24 hr (p < 0.001), but that of CD44 remained unchanged. VCAM-1 expression began to decrease around 1 hr after the initiation of flow and became markedly reduced with time, reaching a minimum after 24 hr. When the cells subjected to flow for 24 hr were returned to stationary state, the reduced VCAM-1 expression was almost completely restored in 72 hr, indicating that the change was reversible. The magnitude of the reduction of VCAM-1 expression was also dependent on the intensity of the wall shear stress applied, ranging from 0 to 7.2 dynes/cm2. These results, demonstrating an explicit down-regulating effect of flow on VCAM-1 expression of cultured ECs, suggested preferential adhesion of leukocytes to ECs at low shear regions at the vascular wall.

Animals↗
PubMed1993

Wall shear stress rather than shear rate regulates cytoplasmic Ca++ responses to flow in vascular endothelial cells.

Recent evidence suggests that the vascular endothelial cell (EC) can sense the flow-rate over its surface and according to the information, regulates not only its own morphology and functions but also those of the surrounding smooth muscle and other tissues. There is now a discussion over which of the following mechanisms actually initiates the signal-transacting response of EC against flow: the mechanical shear deformation of the cell due to flow-oriented wall shear stress (tau), or the diffusional accumulation of vasoactive agonists on the cell surface modulated by wall shear rate (gamma) or both. To identify the relative importance of each mechanism, we examined quantitative changes in the cytoplasmic free Ca++ concentration ([Ca++]i) in cultured EC in the presence of the Ca++ mobilizing agonist ATP, i.e., a second messenger response of the internal signalling system, following the perfusion of two buffers with different viscosities (mu), which relates these factors as tau = mu gamma. The results of in vitro fluorescence photometry in EC with Fura-2 showed that the [Ca++]i level was enhanced with increase in the shear rate but to a greater extent with higher viscosity, and that the [Ca++]i levels at the same calculated level of shear stress were virtually identical, regardless of difference in shear rate and viscosity. This quantitative one-to-one relationship between the shear stress and the second messenger response suggests that wall shear stress rather than wall shear rate is the principal physical factor eliciting EC responses to flow.

Animals↗
PubMed1993

Close correlation between cytoplasmic Ca++ levels and release of an endothelium-derived relaxing factor from cultured endothelial cells.

We studied whether there is a quantitative relationship between free cytosolic Ca++ levels and the release of an endothelium-derived relaxing factor (EDRF) from cultured fetal bovine aortic endothelial cells (EC). EC pretreated with indomethacin were stimulated by the agonists adenosine triphosphate (ATP), bradykinin (BKN), acetylcholine (ACh) and calcium ionophore (A23187) in various concentrations (10(-8)-10(-5) M), and the amount of EDRF released was determined on the basis of endothelium-free rabbit aortic ring relaxation and cultured smooth muscle cell cGMP content. Changes in intracellular Ca++ concentration ([Ca++]i) in response to the same stimuli were determined by photometric fluorescence microscopy using the fluorescent calcium indicator Fura-2. EC stimulation by ATP and A23187 induced dose-dependent increases in both [Ca++]i and the amount of EDRF released. BKN increased both [Ca++]i and EDRF release upon initial exposure (10(-8)M), but there were no further changes at higher concentrations. ACh induced no significant changes in either [Ca++]i or EDRF release. There was a close quantitative correlation between agonist-induced changes in [Ca++]i and the amount of EDRF released (relaxation response in aortic rings and cGMP levels.) (p < 0.001) Removal of extracellular Ca++ eliminated continuous elevation in both [Ca++]i and the amount of EDRF induced by ATP (10(-5)M), BKN (10(-8)M) and A23187 (10(-6)M). These findings suggest that intracellular Ca++ levels are directly linked to the amount of EDRF released, and that extracellular Ca++ is essential for EDRF release because its influx is involved in the continuous elevation of [Ca++]i.

Acetylcholine↗
PubMed1993

[Role of hemodynamic factors in atherogenesis].

Since atherosclerotic lesions are apt to occur at specified regions in the blood vessels, hemodynamic factors, such as shear stress generated by blood flow, have been considered to play a role in atherogenesis. Atheroma, which is characterized by the localized accumulation of lipid and the proliferation of smooth muscle cells in the intima, appears at branching or curving sites of blood vessels, where both geometrical shape and blood flow change suddenly. In such sites, both stagnant and turbulent blood flow can occur and the direction and intensity of shear stress, acting on the vascular wall, changes transiently. Recent studies using cultured endothelial cells (EC) and flow-loading apparati have demonstrated that shear stress modulates various EC functions. Shear stress alters EC macromolecular permeability and affects the production of growth factors, by the EC, which stimulate smooth muscle cell proliferation. Shear stress also exerts an influence on EC turnover, which might be involved in the transport of low-density lipoproteins via leaky junctions. Furthermore, shear stress modulates the interaction between leukocytes and EC by changing the expression or functions of adhesion molecules. It is very likely that changes in EC functions induced by shear stress are involved in atherogenesis, but direct evidence demonstrating the role of shear stress in the initiation of atherosclerotic disease processes is still lacking. Further studies are needed to clarify the role of hemodynamic factors in atherogenesis.

Animals↗
PubMed1993

Blood flow and vascular endothelial cell function.

Vascular endothelial cells (ECs) are not merely a selective permeability barrier between blood and underlying tissue but actively play an important role in maintaining homeostasis of circulation. ECs that have a variety of synthetic, metabolic, secretory and self-adaptive capabilities regulate vascular tonus and interact with other cells such as vascular smooth muscle cells and white cells. Recent evidence suggests that these functions are affected by shear stress on the endothelial wall, which is a rheological force shearing the luminal surface of the blood vessel when a viscous fluid such as blood flows over it. Wall shear stress reportedly regulates adaptive vessel growth and angiogenesis, and might be a local risk factor in the pathogenesis of atherosclerosis. Shear stress also modulates the production of vasoactive substances such as endothelium-derived relaxing factor, prostacyclin, histamine and endothelin, and regulates macromolecule permeability and endocytosis. More recent studies have shown that shear stress exerts an influence on the expression of mRNA such as tissue plasminogen activator mRNA. These facts suggest that ECs serve as mechanoreceptors by which changes in blood flow or shear stress are recognized by the EC and the signal is transmitted to intracellular organelles. It has been indicated so far that intracellular Ca2+ and the membrane potential might be involved in the shear stress-sensing mechanism of ECs. Knowledge of EC biomechanics, i.e. the EC response to shear stress, will help us to understand the mechanism not only of blood flow-dependent vessel growth and remodeling but also atherogenesis.

Animals↗