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S Takaichi

Publications and source records attributed to S Takaichi.

At least 55 records · Page 3Linked to original sources
PubMed1993

Ultrastructural studies on the phenotypic modulation of human intimal smooth muscle cells.

The present study was carried out to clarify the mechanism of intimal thickening at the ostia of celiac and superior mesenteric arteries. The cell components involved in the process were analyzed under electron microscope. Autopsy samples from cases without significant atherosclerotic diseases were examined and the percentages of smooth muscle cells in either synthetic or contractile state, macrophages, and foam cells in the intima of mesenteric and celiac arteries were calculated. Smooth muscle cells in the synthetic state were predominant in the proximal region and those in the contractile state were predominant in the distal region. Few macrophages were present in both regions. The intima in the proximal and distal regions of celiac arteries in autopsy samples was further divided into three layers and the percentages of various smooth muscle cell phenotypes in each layer were calculated and compared in patients at different ages. In the proximal region, the phenotype of the smooth muscle cells changed from the synthetic to the contractile state from the deeper to the superficial layers with the advance of age. In the distal region, the contractile state was dominant regardless of the age. These results suggest that the phenotypic modulation of human intimal smooth muscle cells is reversible dedifferentiation-redifferentiation process; this phenomenon plays an important role in the initiation of atherosclerosis.

Adolescent↗
PubMed1993

The role of vascular smooth muscle cell phenotypic modulation at the aortic branch in atherogenesis.

To elucidate the mechanism of the development of atherosclerosis, we have investigated the cell population of phenotypes of contractile (C-SMC) and synthetic (S-SMC) states of SMCs at proximal and distal areas of bifurcation of the celiac and superior mesenteric arteries in children and young persons by transmission electron microscopy. The previous studies in patients with hypercholesterolemia and who were young indicated that percentages of proximal area at bifurcation of both arteries were greater than that of C-SMC (P 0.01), and that C-SMCs at distal area were less than that of S-SMC (P 0.05). Ultrastructurally, SMCs at proximal area were S-SMCs containing many synthetic organelles and intermediate filaments. On the other hand, those at distal area were C-SMCs containing actin, myosin, dense bodies and microtubules. In the present study, we have ascertained that the phenotypic modulation of SMCs in the intima and media might correlate to the physico-medial relationship between SMCs and elastic tissues. In this communication, we have observed that the intimal SMCs transformed their phenotypes from the internal elastic layer (S-SMC) to the superficial layer (C-SMC), and that the medial SMCs in the arteries of the young clearly consisted of two types: one type adhered to the elastic layer and the other type existed with the separated one. The difference between both areas in the relatively young need to be observed in detail from now on. In summary, the vascular SMCs and the elastic lamina are considered to contribute to the subsequent phenotypic modulation and their migration of SMCs.

Adolescent↗
PubMed1991

Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide.

Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.

Animals↗
PubMed1991

Dose dependency of germanium-dioxide-induced nephrotoxicity in rats.

The dose dependency of germanium dioxide(GeO2)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO2, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with higher dose of GeO2. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO2. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO2. The present study demonstrates that GeO2-induced nephrotoxicity develops dose dependently.

Animals↗
PubMed1991

The role of vascular smooth-muscle cells in atherogenesis: phenotypic modulation of the medial smooth-muscle cells in the aortic bifurcation.

To elucidate the mechanism of migration of vascular smooth-muscle cells (SMCs) from media to intima, we have investigated the phenotypic modulation of the medial SMC at bifurcation of the celiac artery in 5 children and 3 young persons using a transmission electron microscope. We counted the number of separated SMCs from the elastic layers, although the medial SMCs are fundamentally attached to the elastic fibers, and are still contractile in their phenotypes. Both proximal and distal portions revealed that SMCs in the media were more or less present in the separated state and were ultrastructurally consistent with the synthetic state of SMC in the proximal area and the contractile state in distal areas. In order to migrate from media to intima, medial SMC should separate from the elastic layers and transform their phenotypes. In this paper, we examined the relationship between vascular SMCs and elastic layers in the media and ascertain that it was responsible for the contribution to the subsequent phenotypic modulation and their migration of medial SMCs.

Adolescent↗
PubMed1988

Binding and receptor down-regulation of a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells.

Binding of a novel endothelium-derived vasoconstrictor endothelin (ET) and the regulation of its receptor were studied in cultured rat vascular smooth muscle cells. 125I-labeled-ET bound to the cells was resistant to acid extraction and the majority of the acid-resistant compartment was extractable with chloroform/methanol with minimal degradation. Autoradiographic studies using electron microscopy revealed that the grains were predominantly localized in the plasma membranes, but some were adjacent to and within the lysosome. Pretreatment with ET resulted in a substantial reduction of ET receptor number without changing its binding affinity. ET-induced increase in cytosolic free Ca2+ levels [( Ca2+]i] was absent or attenuated in the ET-pretreated cells. These data suggest that tight association of ET with its receptor is due to a strong interaction of its hydrophobic domain with the membrane lipids and/or its internalization within cells and that down-regulation of ET receptor is functionally linked to decreased ET-induced [Ca2+]i response.

Animals↗
PubMed1988

Effect of probucol on macrophages, leading to regression of xanthomas and atheromatous vascular lesions.

To explain the strong effect of probucol on xanthomas, the drug's effect on lipid storage in macrophages in the presence of denatured low-density lipoprotein (LDL) was studied. Two macrophage cell lines, UE-12 and THP-1, were used. Those cells stored lipids and became foam cells when they were incubated with acetylated LDL (acetyl-LDL). When probucol was added into the medium either in ethanolic solution or in the form bound to LDL, the storage of cholesterol and other lipids and the development of macrophages into foam cells were greatly suppressed. Two functions of probucol should be considered: (1) It inhibited the uptake of acetyl-LDL by macrophages; and (2) it enhanced the release of cholesterol from these cells. Cells were first incubated with probucol. After the cells were washed with fresh medium, the radiolabeled acetyl-LDL was added to the medium and the degradation of acetyl-LDL was measured. Increasing the concentration of probucol led to a decrease in degradation of acetyl-LDL by macrophages. Probucol also suppressed the uptake of albumin. Macrophages were incubated with acetyl-LDL, washed once, then incubated with or without probucol and high-density lipoprotein (HDL). Addition of HDL caused a rapid decrease in cholesterol content in the cells, and this phenomenon was enhanced by probucol for both kinds of cells. The secretion of apolipoprotein E was also stimulated by the addition of probucol. These 2 sets of experimental results suggest that probucol prevents lipid storage in macrophages by both suppressing the uptake and stimulating the release of cholesterol and other lipids into or from the macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1986

Probucol prevents lipid storage in macrophages.

Effects of probucol on lipid storage in macrophages in vitro in the presence of acetylated low density lipoprotein (acetyl-LDL) were observed using macrophage-like cells (UE-12) established from a human histiocytic lymphoma cell line (U-937). Under ordinary light microscopy as well as under electron microscopy we found that probucol added to the medium, either in ethanolic solution or bound to LDL, markedly prevented the development of macrophages into foam cells. Microscale enzymatic assay of cholesterol also showed that the intracellular accumulation of esterified cholesterol caused by acetyl-LDL was markedly decreased by the addition of probucol. The concentration of probucol added to the medium was almost comparable to the plasma concentration of the drug usually obtained in patients under treatment with probucol. The possibility that probucol interferes with the binding of acetyl-LDL to the receptors on the cell surface was suggested. The results of the present investigation coincide with the clinical findings that probucol causes a more marked regression of xanthomas than would be expected from the extent of lowering of LDL cholesterol.

Cell Line↗
PubMed1985

Thrombus formation by the application of thrombin to the outer surface of mouse mesenteric vein: comparison with the application of ADP.

Mesenteries of mice under anesthesia were stretched over an inverted microscope. A micropipette filled with solution containing various concentrations of ADP or thrombin was brought into contact with the outside of a mesenteric vein by micromanipulation, and then poured over the outer surface of the vein. Morphological characteristics of the thrombi and the time needed for thrombus formation were examined. Application of either thrombin or ADP to the adventitia of mesenteric veins caused thrombus formation. Although thrombi by application of ADP seemed to be anchored by direct adhesion of platelets to the exposed subendothelium, thrombi by application of thrombin seemed to be anchored by deposited fibrin.

Adenosine Diphosphate↗
PubMed1985

Binding, internalization, and degradation of atrial natriuretic peptide in cultured vascular smooth muscle cells of rat.

Binding, internalization, and degradation of 125I-labeled-rat atrial natriuretic peptide (rANP) were studied in cultured rat aortic vascular smooth muscle cells (VSMC). At 37 degrees C, 125I-labeled-rANP rapidly bound to VSMCs, but the cell-bound radioactivity rapidly decreased upon subsequent incubation, while the binding was slow at 4 degrees C, reaching to an apparent equilibrium after 6 hrs. The cell-bound 125I-labeled-rANP at 37 degrees C is rapidly dissociated from VSMC (t 1/2: approximately 40 min) with the appearance of degradaded product(s) of radioligand in the medium, whereas the degradation was minimal at 4 degrees C. This degradative process was blocked by inhibitors of metabolic energy production (azide, dinitrophenol), inhibitors of lysosomal cathepsins (leupeptin, pepstatin), and lysosomotropic agents (NH4Cl, chloroquine, lidocaine, methylamine, dansylcadaverine), but not by inhibitors of serine or thiol proteases. 125I-labeled-rANP initially bound to the cell-surface was rapidly internalized, and delivered to lysosomal structures, which was confirmed by autoradiographic studies. These data indicate that rANP, after binding to the cell-surface receptors, is rapidly internalized into the cells through receptor-mediated endocytosis, and subsequently degradaded by lysosomal hydrolases.

Animals↗
PubMed1984

[Experimental heart transplantation in dogs--preservation of isolated hearts for 36 hours by retrograde coronary sinus microperfusion].

In this study, the method of preserving isolated canine hearts for transplantation was established. The newly-developed method is named retrograde coronary sinus microperfusion technique. Canine hearts were arrested and cooled to 4 degrees C by means of normograde coronary perfusion with Collins' solution containing 10% fluorocarbon (FC) in order to avoid myocardial damage during warm ischemic time. Then, the hearts, immersed in Collins' solution, were retrogradely perfused through a coronary sinus at a rate of 60 ml/hr or 30 ml/hr with above-mentioned solution. After preservation for 36 hours, heterotopic heart transplantation was performed in an abdominal cavity of a recipient dog. The 36 hour-preserved hearts restored their cardiac beat after reperfusion with recipient blood. Histological observation did not show any abnormal findings in these preserved hearts. In order to evaluate the cardiac functions of preserved hearts for 24 to 36 hours, left ventricular end-systolic pressure-volume ratio (Emax) and end-diastolic pressure-volume relation were measured. Both were well restored in 24 hour-preserved hearts. The 36 hour-preserved hearts resulted in Emax within a satisfactory range, while end-diastolic pressure was elevated in all cases. This was markedly impaired with infusion of isoproterenol. These results strongly suggested that transplantation using 24 hour-preserved hearts could be performed well. On the other hand, the 36 hour-preserved hearts were considered to function satisfactorily under careful management after grafting. The retrograde coronary sinus microperfusion method developed here was found to be useful for a distant heart procurement.

Animals↗
PubMed1981

Procedures and conditions for application of the pyridine hemochrome method to photosynthetically grown cells of Rhodopseudomonas sphaeroides.

The conditions and pretreatments required in the conventional pyridine hemochrome method were re-examined for application of the method to the measurement of protoheme and heme c contents in photosynthetically grown cells of Rhodopseudomonas sphaeroides. The amounts of hemes were calculated from two kinds of difference absorbances between two wavelengths of the redox difference spectrum of the pyridine hemochromes prepared from the disrupted cells. Extraction of photosynthetic pigments from the cells with organic solvents and separation of hemes in hemoproteins into the protoheme and the heme c fractions by the differential extraction of hemes with an acidified organic solvent were omitted.

Dithionite↗
PubMed1978

Amino acid sequences of two ferredoxins from pokeweed, Phytolacca americana.

The amino acid sequences of two ferredoxins isolated from pokeweed, Phytolacca americana, were determined. Tryptic peptides of maleyl-carboxymethyl-ferredoxin I and carboxymethyl-ferredoxin II were prepared and analyzed. The large peptides were further digested with staphylococcal protease and chymotrypsin. Ferredoxins I and II were composed of 96 and 98 amino acid residues, respectively. Though ferredoxin I lacks tryptophan and methionine, ferredoxin II contains both of them. In a comparison of the amino acid sequences with those of other higher plant ferredoxins, ferredoxin I is one residue shorter than others at the carboxyl-terminus and ferredoxin II one longer than others at the amino-terminus. Ferredoxins I and II differ in 23 sites from each other and in 27 to 37 sites from other higher plant ferredoxins. This suggests that duplication of the ferredoxin gene occurred after the divergence of pokeweed from other higher plants. A phylogenetic tree including all other ferredoxins was constructed.

Amino Acid Sequence↗