Biomedical subjects

S Jimi

Publications and source records attributed to S Jimi.

At least 55 records · Page 3Linked to original sources

PubMed1995

Oxidized low density lipoprotein stimulates collagen production in cultured arterial smooth muscle cells.

We examined the interactive effect of oxidized low density lipoprotein (LDL) and ascorbic acid on collagen production in cultured smooth muscle cells (SMCs). Porcine aortic SMCs were incubated with 50-200 micrograms/ml of human LDL with/without 5 microM Cu2+ for 24 h. Collagen production was assayed by successive salt precipitation at acidic and neutral pH after pepsin digestion of 3H-proline-labeled collagenous protein. Oxidation of LDL was evaluated by electrophoresis and by the level of thiobarbituric acid reactive substances (TBARS). Ascorbic acid reduced the oxidation of LDL + Cu2+ (53% reduction). In the presence of ascorbic acid, no differences were noted in collagen production between LDL and LDL + Cu2+. Without ascorbic acid, collagen production with LDL + Cu2+ was increased dose-dependently up to 6-fold with 150 micrograms/ml LDL, while no such effects were observed at any doses of native LDL. The addition of butylated hydroxytoluene to LDL + Cu2+ strongly suppressed oxidation (88% reduction), and significantly reduced collagen production close to that seen with native LDL. These results indicate that oxidized LDL stimulates collagen production in SMCs, while native LDL does not. Therefore, oxidized LDL may play a direct role in stimulating collagen production in SMCs, which could lead to collagenosis in atherosclerosis.

Animals↗

PubMed1995

Nonenzymatic glycation and extractability of collagen in human atherosclerotic plaques.

The relationship between the extractability of collagen by enzymatic digestion and the degree of nonenzymatic glycation of collagen was examined in the aorta and skin from 38 subjects without diabetes mellitus (mean age: 62.3 +/- 20.2 years). Samples were obtained from the aortic media (M), lesion-free intima (I), atherosclerotic intima (A) and dermis of the skin (S). Collagen was extracted first by incubation with 1/50 (enzyme/substrate weight ratio) pepsin at 4 degrees C for 24 h (P-fraction) and then by incubation with 1/10 (enzyme/substrate weight ratio) pepsin at room temperature for 24 h (EP-fraction). The pepsin-insoluble precipitates were digested by incubation with 270 units of bacterial collagenase at 37 degrees C for 24 h (PIS-fraction). Collagen contents, ketoamines and collagen-linked fluorescence (CLF) were measured in each fraction. The amount of ketoamines and the level of CLF correlated inversely with the susceptibility of collagen to pepsin digestion in various tissues, including M, I, A and S. These values were highest in both the P- and EP-fractions of M, which contained the least amount of collagen extracted by pepsin digestion. In contrast, they were lowest in S, where the concentration of collagen extracted by pepsin digestion was greatest among all of the tissue samples. Atherosclerotic intima (A) and aortic media (M) showed an age-related increase in the total amount of collagen digested with pepsin and collagenase, which depended mainly on an increase in the content of pepsin-insoluble collagen. Although the total amount of collagen did not increase with advancing age in I or S, collagen in I and S became progressingly resistant to pepsin digestion. These results suggest that the age-related decrease in the susceptibility of collagen to pepsin digestion may be due to nonenzymatic glycation in atherosclerotic lesions as well as normal tissues, including the aortic media, lesion-free intima and skin. The level of CLF significantly increased with age in the P-fraction and/or EP fraction of M, I and S. However, there was no relationship between the level of CLF and the subject's age in A. Thus, the accumulation of advanced glycation endproducts (AGEs) on collagen fibers may be partially responsible for the increase in collagen matrix in atherosclerotic lesions of subjects without diabetes mellitus.

Adolescent↗

PubMed1995

A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease.

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.

Adolescent↗

PubMed1995

Combined effects of pravastatin and probucol on high-density lipoprotein apolipoprotein A-I kinetics in cholesterol-fed rabbits.

The combined effects of pravastatin and probucol on high- density lipoprotein (HDL) apolipoprotein (apo) A-I kinetics in cholesterol (Ch)-fed rabbits were investigated. Japanese White rabbits were treated with 0.15% pravastatin and 0.5% Ch (group 1) or 0.15% pravastatin plus 1% probucol and 0.5% Ch (group 2) for 2 months. After treatment, the serum total cholesterol levels in groups 1 and 2 had significantly (p < 0.01) increased (37.4 +/- 6.7 mg/dl vs 117.1 +/- 46.4 mg/dl, and 31.4 +/- 4.9 mg/dl vs 143.0 +/- 84.5 mg /dl, respectively). The serum HDL-cholesterol levels in both groups decreased (18.2 +/- 2.8 mg/dl, vs 16.2 +/- 3.7 mg/dl p < 0.01 for group 1; 18.2 +/- 1.9 mg/dl vs 15.5 +/- 4.5 mg/dl, ns for group 2). Apo A-I kinetics were assessed by injecting (125)I-labeled HDL intravenously into both groups of rabbits, and taking blood samples periodically for 6 days. Kinetic parameters calculated from apo A-I specific radioactivity decay curves showed that the apo A-I fractional catabolic rates in rabbits fed pravastatin and Ch (group 1) were significantly less than those in rabbits fed pravastatin plus probucol and Ch (group 2) (0.546 +/- 0.017 /day vs 0.730 +/- 0.126 /day, p < 0.05), while the synthetic rate of apo A-I was lower in group 2 than in group 1 (14.76 +/- 1.71 mg/kg per day vs 11.21 +/- 2.38 mg/kg per day, respectively, p < 0.01). These data indicate that pravastatin and probucol have different effects on HDL-apo A-I kinetics in a diet which includes cholesterol.

Animals↗

PubMed1995

Reduced coronary vasodilation in patients with familial hypercholesterolemia following intracoronary injection of isosorbide dinitrate.

To clarify the relationship between the dilatation of angiographically non-stenotic coronary artery segments in response to isosorbide dinitrate (ISDN), and serum lipids, 5 coronary segments in 7 patients with familial hypercholesterolemia (FH) and 43 patients with non-familial hypercholesterolemia (non-FH), who had either 1- or 2-vessel coronary heart disease, were investigated. The serum total cholesterol level was significantly greater in FH than in non-FH. Before and after the direct intracoronary injection of ISDN, coronary diameter was measured by a computer-assisted coronary angiography analysis system. The order of the dilative responses in coronary segments in non-FH patients (segments: #5 > #11 > #6 > #13 > #7) was exactly the same as the order of their original diameters, while the ratio of the increase in diameter (after/before ISDN injection) did not differ among any of the segments (mean: 1.08-fold increase). In the non-FH group, no correlation was found between the serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol, or high-density lipoprotein-cholesterol, and the ratio of the coronary diameter after and before injection of ISDN. Moreover, hypercholesterolemia in non-FH did not affect the coronary dilative response to ISDN injection. In the FH group, although the original diameter of each segment did not differ from that in the non-FH group, the ratio of the diameter after and before injection of ISDN was significantly smaller in FH than in non-FH (p < 0.01). These results suggest that a non-stenotic coronary artery in FH has a lower capacity for vasodilation in response to ISDN. Although hypercholesterolemia was excluded as a factor which may suppress the capacity for coronary dilation in non-FH, spontaneous hypercholesterolemia in FH may affect medial smooth muscle functions of the coronary artery.

Adult↗

PubMed1995

[Aging of aorta and atherosclerosis--role of nonenzymatic glycation of collagen].

In order to clarify the role of the nonenzymatic glycation of the collagen matrix in aging of the aorta and atherogenesis, we studied the relation between ketoamine or advanced glycation end-products (AGEs) and the solubility of collagen in human skin and aorta. AGEs were measured as a collagen-linked fluorescence (excitation wavelength: 370 nm. emission wavelength: 440 nm). There was a positive correlation between the level of AGEs and subjects' age in skin and aortic media. Collagen became more insoluble with increase in the amount of ketoamine and AGEs. Collagen was more resistant to pepsin digestion in atherosclerotic intima than in other tissues including aortic media, lesion-free intima and skin. Diabetic rats showed an accumulation of collagen in aortic media at 28 weeks after an injection of streptozotocin. Moreover, they increased the percentage of insoluble collagen to total collagen and the amount of AGEs binding to insoluble collagen in aortic media. In contrast, the amount of ketoamine of insoluble collagen was increased in diabetic rats at 16 weeks as compared to control. There was no difference in DNA contents of cultured smooth muscle cells between glycolaldehyde-modified and non-modified matrices. However, the activity of type I collagenase (inactive form) of smooth muscle cells decreased on glycolaldehyde-modified type I collagen as compared to that on non-modified collagen. These results suggest that AGEs contribute to the accumulation of collagen in atherosclerotic lesions and aged aorta through the insolubility of collagen and the inhibition of collagenase activity of smooth muscle cells.

Adult↗

PubMed1994

Plasma HDL levels are regulated by the catabolic rate of large particles of lipoprotein containing apo-A-I.

Lp-A-I was isolated by immunoaffinity chromatography and then separated into two fractions of large and small Lp-A-I particles by conventional ultracentrifugation with a cut-off density of 1.125 g/ml. The large and small particle-rich fractions were then radiolabeled with [125I]-Na and [131I]-Na, respectively. Both of the labeled lipoproteins were injected (20 microCi, i.v.) simultaneously into normolipidemic rabbits. The FCR of the large Lp-A-I particles was much less than that of the small Lp-A-I particles (0.801 +/- 0.026/day vs. 2.227 +/- 0.067/day, P < 0.0001). These data indicate that the two particles have distinctly different metabolic pathways and that the lower FCR of larger Lp-A-I particles can effectively raise plasma HDL levels.

Animals↗

PubMed1994

PDGF-like growth factor from SV40-transformed smooth muscle cells promotes growth in an autocrine or paracrine manner.

We investigated the growth characteristics of smooth muscle cells transformed by oridefective simian virus 40 plasmid DNA (TSMCs). TSMCs demonstrated a significantly higher proliferative activity when compared with nontransformed smooth muscle cells (SMCs). The SMCs were not able to proliferate in media with 5% plasma-derived serum (PDS) instead of fetal bovine serum, while TSMCs grew under this condition. When the DNA synthesis of quiescent SMCs was reinitiated by the addition of serum or platelet-derived growth factor (PDGF), the amount of [3H]thymidine incorporation into DNA varied with the concentrations of serum or PDGF and decreased on type V collagen compared with the other collagen substrates. In contrast, the TSMCs showed no differences in the amount of [3H]thymidine incorporation into DNA among the various concentrations of serum or PDGF and different types of collagen. When quiescent SMCs were cocultured with TSMCs, they showed a remarkable increase in the amount of [3H]thymidine incorporation into DNA, which was most intensively inhibited by type V collagen. These results suggest that TSMCs can promote the growth of TSMCs and SMCs in either an autocrine or paracrine manner and that they proliferate independently of the collagen matrices. Trapidil, a pyrimidine derivative that may inhibit the action of PDGF, decreased the number and cAMC levels of TSMCs in the media with 5% PDS in a concentration-dependent manner. The addition of polyclonal anti-PDGF-B antibody induced up to 59.5% inhibition of enhancement of DNA synthesis of SMCs cocultured with TSMCs. The level of cyclic adenosine monophosphate (cAMP) increased in the TSMCs compared with the SMCs. There was, however, no difference in the cAMP levels of either cells between the various types of collagen. Thus, the release of PDGF-like growth factor and an accumulation of cellular cAMP may be related to an increased DNA synthesis of TSMCs.

Animals↗

PubMed1994

Low density lipoproteins bind more to type I and III collagens by negative charge-dependent mechanisms than to type IV and V collagens.

The accumulation of low density lipoprotein (LDL) in the arterial intima is an important characteristic of atherosclerosis. We investigated the mechanisms by which LDL binds to different types of collagen. The binding activities of 125I-labeled human native LDL (nLDL) and copper-oxidized LDL (oxLDL) with different collagen gels prepared in type I collagen-based mixtures with types I, III, IV and V (I+I, I+III, I+IV and I+V, respectively) were examined. A concentration of 20 micrograms LDL protein/150 micrograms collagen/well was used. The diffusion of both nLDL and oxLDL into the collagen gels reached an equilibrium after 48 h. All of the collagen gels showed the same rates of diffusion with both LDLs. The binding activities of oxLDL were significantly greater than those of nLDL (P < 0.001%), while the binding activities for both LDLs followed the order I+I and I+III > I+V > I+IV. However, the increased binding rate of oxLDL compared to nLDL was 1.66 for I+IV, 1.50 for I+V, 1.33 for I+I and 1.19 for I+III. When a 10-fold higher dose of NaCl (1 M) was added to the oxLDL medium, the binding rate of oxLDL was reduced (rate of reduction: 52% (I+I), 48% (I+III), 35% (I+IV), 13% (I+V)). These results suggest that oxLDL binds more to type I and III collagens by negative charge-dependent mechanisms than to type IV and V collagens. Therefore, types I and III collagens may play an important role in trapping LDL, especially oxLDL. Therefore, oxidatively modified LDL may contribute to atherogenesis due to its longer retention in the arterial wall.

Arteriosclerosis↗

PubMed1994

Oxidized LDL induces an increase in the relative collagen synthesis of rabbit aortic smooth muscle cells.

Cell degeneration and collagenosis are the main features in atherosclerotic plaque. We examined the effects of human low density lipoprotein (LDL) on cultured rabbit aortic smooth muscle cells (SMCs). Copper oxidized LDL (LDL+Cu) injured the SMCs more than did native LDL. Cytotoxicity of oxidized LDL was prevented by the simultaneous addition of butylated hydroxytoluene (BHT) and ethylenediamine tetraacetic acid. Collagen synthesis increased up to 6 fold after incubation with 200 micrograms protein/ml of both native and oxidized LDL compared with that incubated in bovine serum albumin. Noncollagen protein synthesis was significantly reduced by oxidized LDL when compared to that by native LDL. Therefore, oxidized LDL increased the relative collagen synthesis (3.33%) to a greater extent than did native LDL (0.72%). By adding BHT to LDL+Cu, the elevated relative collagen synthesis was reversed due to the restoration of noncollagen protein synthesis while it also inhibited LDL peroxidation as evaluated by the formation of malondialdehyde (MDA). However, sodium MDA (up to 200 microM) did not induce either cytotoxicity or an increase of relative collagen synthesis. We therefore conclude that oxidized human LDL enhanced the relative collagen synthesis coinciding with the induction of injury in cultured aortic SMCs, however free MDA may not be the component responsible for these effects.

Animals↗

PubMed1994

[Tangier disease].

Tangier disease, a familial HDL-deficiency syndrome, was first reported by Fredrickson et al. in 1961. Since then, a great deal research on the mechanism of HDL-deficiency in this disease has been done from the prospective of lipoprotein compositions, in vivo HDL kinetics, cell and receptor interactions and genomic DNA analysis. These studies have found a relatively increased fractional catabolic rate of apo HDL with essentially no change in the synthesis of apo HDL. As yet, no structural defect has been found in the apo A-I gene. However, there have been reports of irregular lipid metabolism and of disorders in the Golgi apparatus and lysosome processing. Interestingly, the frequency of coronary heart disease is low in patients with Tangier disease. In this report, we describe the clinical and biochemical characteristics of Tangier disease and suggest some possible mechanisms for preventing coronary heart disease.

Apolipoproteins↗

PubMed1994

Comparative effects of an angiotensin-converting enzyme inhibitor and an angiotensin II antagonist in Dahl rats.

The antihypertensive, cardioprotective, and renoprotective effects of a nonpeptide angiotensin II antagonist (AIIA, CV-11974) and an angiotensin-converting enzyme inhibitor (CEI, captopril) were compared in Dahl salt-sensitive rats. Six-week-old male rats received a high-salt diet (4% NaCl) and were divided into control, CEI, and AIIA groups. The CEI group received captopril (15 mg/kg/day) and the AIIA group received CV-11974 (0.72 mg/kg/day), an active metabolite of the AIIA TCV-116, for 4 weeks by continuous subcutaneous infusion. After 4 weeks, systolic blood pressure (SBP) was significantly lower in the treatment groups than in the control group. The heart weight/body weight ratio and urinary protein excretion were reduced in the treatment groups, and renal damage (glomerular sclerosis score) was reduced by approximately 50%. CV-11974 and captopril were comparable in reducing BP, cardiac hypertrophy, and renal damage, suggesting that the renin-angiotensin (R-A) system is involved in elevating BP and promoting cardiovascular damage, despite suppression of the R-A system in this model. The antihypertensive effect of CEI may be due primarily to inhibition of the action of angiotensin II, while other effects, e.g., potentiation of the kinin system, may be less important.

Angiotensin Receptor Antagonists↗

PubMed1993

Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus.

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without diabetes mellitus (DM), in 101 patients with diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls, respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes mellitus. We assumed the differences in apo(a) phenotypes detectable with our method reflected consecutive differences in molecular weights of apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Porcine vascular smooth muscle cells immortalized with SV40 ori-defective DNA: characteristics of cell growth and collagen synthesis.

A cell line derived from medial smooth muscle cells (SMC) was established from the porcine coronary artery by transfection with ori-defective simian virus 40 plasmid DNA (SV40 DNA). The characteristics of transfected cells (SV40-SMC) such as cell growth, collagen and non-collagen syntheses were investigated. SV40-SMC expressed SV40 large T antigen, c-myc and c-myb encoded proteins in the nuclei. SV40-SMC demonstrated a 'hills and valleys'-like arrangement in overconfluence and actin filaments upon immunofluorescent staining. Under electron microscopic observation, SV40-SMC had larger amounts of synthetic organelles and smaller amounts of filament bundles than those of SMC. SV40-SMC demonstrated three times higher growth activity and 4.4 times greater cellular density than SMC. Smooth muscle cells did not grow in media containing 5% plasma derived serum (PDS) instead of normal serum, whereas SV40-SMC proliferated in this medium. SV40-SMC did not grow in soft agar gel, while HeLa S3 cells, a cell line of human cervical carcinoma, formed colonies in this gel. By immunofluorescent (IF) staining, collagen phenotypes I, III, IV and V were detected in both SV40-SMC and SMC. However, protein synthesis including collagen and non-collagen was higher in SV40-SMC than in the control sample. It was concluded that SV40-SMC were a continuous cell line for vascular SMC regarding morphological characteristics, and demonstrated a higher growth activity, with increased collagen and non-collagen syntheses. This cell line is useful for the investigation of atherogenesis in relation to a proliferation of SMC and an accumulation of extracellular matrices in vascular intima.

Agar↗

PubMed1993

[The role of collagen matrix in atherogenesis].

The different types of collagen including Types I, III, IV, V, VI and VIII are distributed in the artery. The atherosclerotic lesions, such as fatty streaks and atheromatous plaques, are characterised by an increase in types V and VI, which are localized in the region with a deposition of LDL and an infiltration of macrophages. Vascular smooth muscle cells interact with various types of collagen. Collagen matrices induce an enhancement of differentiation and suppression of cellular proliferation of "normal" smooth muscle cells. However, transformed smooth muscle cells fail to interact with various types of collagen. These results suggest that the interaction between vascular cells, including smooth muscle cells, macrophages and endothelial cells and collagen matrices is important in atherogenesis.

Adolescent↗

PubMed1992

Type V collagen represses the attachment, spread, and growth of porcine vascular smooth muscle cells in vitro.

We attempted to clarify the effects of various purified extracellular components, including types I, III, IV, and V collagen and fibronectin on attachment, spread, growth, and DNA synthesis of porcine aortic smooth muscle cells (SMCs) in vitro. The number, area and shape index (SI = 4 pi S/L2) of cells attached to different substrates were determined at various intervals of incubation. The cell number and [3H]thymidine incorporation into DNA were measured on the 1st and 6th days of culture. SMCs showed the largest number of attached cells on fibronectin, but the smallest number of attached cells on type V collagen. There was no evidence of effects of the serum in media on the attachment of SMCs to the substrates. The areas of attached SMCs were the largest on fibronectin and the smallest on type V collagen. The shape index of SMCs on fibronectin decreased relative to those on other substrates. On the 6th day in culture, the number and population doubling of SMCs on type V collagen were significantly fewer than those on other substrates. Both the incorporation rate of [3H]thymidine into DNA and the percentage of nuclei labeled with [3H]thymidine were significantly less in the SMCs on type V collagen on the 1st day than those on other substrates. SMCs on types I, III, and IV collagen showed intermediate levels of cell attachment, spread, and growth. These results suggest that attachment, spread, and growth of SMCs are affected mainly by solid phase purified extracellular components and are most strongly suppressed by type V collagen. When DNA synthesis of growth-arrested SMCs was reinitiated by the addition of serum, type V collagen most intensively inhibited the rate and amount of [3H]thymidine incorporation. Flow cytometric analysis demonstrated an increased in the proportion of cells in G0/G1 phase on type V collagen in comparison with that on other substrates. Thus, the antiproliferative effect of type V collagen may relate to inhibition of transition of SMCs from the G0/G1 into the S phase.

Animals↗

PubMed1992

[A case of recurrent endometrial cancer successfully treated with oral administration of etoposide].

A 61-year-old female with recurrent endometrial cancer (serous papillary adenocarcinoma) was treated with etoposide because the pelvic tumor progressively increased in size with external beam irradiation. The etoposide (25 mg/day) was given orally for 10 days; the tumor decreased in size. And after an additional two courses of etoposide for 8 and 4 days, respectively, the tumor disappeared and the serum CA 125 level came to within normal limits. Because of moderate nausea and vomiting the etoposide could not be given for 14 days in the first 3 courses. Myelosuppression was not evident. Ten courses of etoposide (for 14 consecutive days a month) were followed without gastro-intestinal side effects, and the patient is alive with no evidence of recurrence at this writing. This case suggests that oral administration of etoposide may be effective for a patient with recurrent endometrial cancer, and this treatment could be administered on an outpatient basis.

Administration, Oral↗

PubMed1991

The effect of cholesterol on the accumulation of intracellular calcium.

Cholesterol/egg phosphatidylcholine (PC) liposomes (1:1 or 4:1, M/M), in which the absolute amount of PC was adjusted to be the same, were incubated with cultured bovine arterial smooth muscle cells for up to 8 h at 37 degrees C. The effect of increased cellular cholesterol on the accumulation of intracellular calcium in these cells was studied. The results indicate that the intracellular calcium content, measured by Fura-2/AM, was increased 2.3-fold by incubation with 4:1, cholesterol/PC liposomes. Kinetic analysis using 45Ca2+ indicated that the increased calcium influx was due to increase of pool size, not from a change of rate constant. (Ca2+ + Mg2+)-ATPase activity was decreased by 4:1, cholesterol/PC liposomes. The molar ratio of cholesterol/phospholipids in the cell membranes was directly proportional to that in liposomes. No change in phospholipid composition was noted. We suggest that the accumulation of intracellular calcium was a composite result due to the altering effect of inserted cholesterol on surface area, and to direct interactions between cholesterol and the proteins of the Ca2+ channel and (Ca2+ + Mg2+)-ATPase.

Animals↗