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S L Hong

Publications and source records attributed to S L Hong.

At least 37 records · Page 2Linked to original sources
PubMed1984

Favorable balance of prostacyclin and thromboxane A2 improves early patency of human in situ vein grafts.

Graft thrombosis soon after reconstruction remains a major obstacle to the use of reversed vein grafts in infrapopliteal reconstruction. Our clinical experience with in situ vein grafts corroborates Leather's results by demonstrating an overall graft patency of 95% below the knee at 1 year and 94% in the infrapopliteal group. It has been postulated that this improved early patency rate of in situ vein grafts is the result of more optimal preservation of the endothelium of the vein graft. To investigate this hypothesis, human saphenous veins were handled by an in situ and a reversed technique. The intact vein segments were then tested for luminal production of prostacyclin and thromboxane A2 and fixed for scanning electron microscopic analysis of the surface morphology. This study demonstrated that endothelial cell prostacyclin release is enhanced in human in situ vein segments but not in reversed vein segments. In addition, luminal production of thromboxane A2 is significantly greater in the reversed than in the in situ vein segments. These findings are associated with marked endothelial structural damage in the reversed veins and minimal endothelial disruption in the in situ veins. Therefore the ratio of the antiaggregatory vasodilator prostacyclin to the proaggregatory vasoconstrictor thromboxane A2 is significantly more favorable for the in situ vein segment than for the reversed vein segment. The observed excellent early patency of the in situ vein grafts in our poor-risk patient population may in part be the result of this favorable balance of prostacyclin and thromboxane A2 and the more optimally preserved endothelial morphology.

Aged↗
PubMed1984

Luminal release of prostacyclin and thromboxane A2 by arteries distal to small-caliber prosthetic grafts.

Myointimal hyperplasia distal to prosthetic grafts may be due to a local imbalance of prostacyclin and thromboxane A2 that exaggerates platelet adherence. This study evaluated prostacyclin and thromboxane A2 production by arteries distal to prosthetic grafts. In 12 dogs, control segments of both iliac arteries were excised and a 5 cm segment of polytetrafluoroethylene was grafted end to end. One iliac artery was circumferentially dissected from the distal anastomosis to the inguinal ligament. The contralateral artery was not dissected. Of the 24 grafts, 19 remained patent and the arteries distal to these grafts were studied. After excision, each artery was analyzed for its ability to produce prostacyclin and thromboxane A2. Our data indicate that the luminal surface of a normal artery spontaneously produces both prostacyclin and thromboxane A2 and that the arterial wall distal to a prosthetic graft produces increased levels of these arachidonic acid metabolites. However, only those arteries not surgically dissected maintain a normal balance of prostacyclin and thromboxane A2. The dissected artery may thus be more susceptible to platelet interaction and myointimal hyperplasia.

Animals↗
PubMed1984

Abnormal VIII: von Willebrand factor patterns in the plasma of patients with the hemolytic-uremic syndrome.

Plasma VIII:von Willebrand factor antigen (VIII:vWF) levels were elevated approximately two- to eightfold in seven patients (three adults and four children) during acute episodes of thrombocytopenia, renal failure, and hemolytic anemia (the hemolytic-uremic syndrome, HUS). In all seven patients, there was an alteration in plasma VIII:vWF patterns during these acute HUS episodes, so that the largest VIII:vWF forms were relatively decreased. Plasma VIII:vWF multimer patterns returned to normal, or nearly to normal, as platelet counts returned to preexisting levels, even in the patients whose recovery of renal function was incomplete and whose plasma VIII:vWF antigen level remained above normal. The sister of one of the HUS patients had a similar clinical prodrome (gastroenteritis) that was not followed by thrombocytopenia or renal failure and was not accompanied by an elevated level or abnormal forms of plasma VIII:vWF. These results suggest that an alteration in VIII:vWF metabolism, distribution, or interaction with platelets is associated with acute HUS episodes. In contrast to patients with chronic relapsing thrombotic thrombocytopenic purpura, none of the HUS patients (either during or after the acute HUS episodes) had a defect in the conversion of unusually large VIII:vWF multimers derived from endothelial cells to the VIII:vWF forms found in normal plasma.

Adult↗
PubMed1983

Inhibition of prostacyclin synthesis in endothelial cells by methylisobutylxanthine is not mediated through elevated cAMP level.

Methylisobutylxanthine (MIX) raised cAMP levels and inhibited prostacyclin synthesis and arachidonic acid release in endothelial cells from both pig aorta and human umbilical vein. These effects were reversible and dose dependent on MIX concentrations. Dibutyryl cAMP (3 mM) alone did not inhibit prostacyclin synthesis or arachidonic acid release. When added with MIX, dibutyryl cAMP did not enhance the inhibition elicited by MIX. MIX inhibited the formation of lysophospholipids, 1,2-diacylglycerol and phosphatidic acid in bradykinin-stimulated pig endothelial cells, suggesting that the inhibition of prostacyclin synthesis resulted from an apparent inhibition of both phospholipase A2 and phospholipase C. Other phosphodiesterase inhibitors, theophylline and mopidamole, also raised cAMP levels and inhibited arachidonic acid release. However, there was no correlation between cAMP levels and these inhibitions. Forskolin, an adenylate cyclase activator, elevated intracellular cAMP levels with no apparent inhibition on prostacyclin synthesis. We conclude that the inhibitory effect of MIX on phospholipase A2 and phospholipase C is probably through mechanisms other than the elevation of the cAMP level.

1-Methyl-3-isobutylxanthine↗
PubMed1981

The activation of phosphatidylinositol-hydrolyzing phospholipase A2 during prostaglandin synthesis in transformed mouse BALB/3T3 cells.

To investigate the type of phospholipase activated by agents that stimulate prostaglandin synthesis, we used transformed mouse cells whose phospholipids were doubly labeled with [14C]inositol and [3H]arachidonic acid. [14C]Inositol was incorporated mostly into the phosphatidylinositol and [3H]arachidonic acid was distributed into the various phospholipids. When these cells were incubated with bradykinin, a stimulator of prostaglandin synthesis, the release of 3H radioactivity from cellular phospholipids and the synthesis of prostaglandin were initiated within seconds and reached a maximum in 40 to 70 s. Analysis of the intracellular lipids revealed a concomitant increase of radioactivity associated with lysophosphatidylinositol, which was detectable within 5 s of incubation with bradykinin and reached a maximum between 40 and 70 s. Lysophosphatidylinositol which could be formed either from a phospholipase A1 or phospholipase A2 reaction, was identified by its chromatographic properties and conversion to glycerophosphorylinositol. We found that the 3H/14C ratio of purified lysophosphatidylinositol was 1/11 of that of phosphatidylinositol, which indicated that lysophosphatidylinositol formed in response to bradykinin is 1-acyl-sn-glycero-3-phosphorylinositol and most probably is formed from a phospholipase A2 deacylation of phosphatidylinositol (a phospholipase A1 deacylation would result in the formation of lysophosphatidylinositol of a 3H/14C ratio similar to phosphatidylinositol). Furthermore, we did not detect between control and stimulated cells any significant difference in the level of several phospholipase C metabolites including inositol phosphate, diglyceride, and phosphatidic acid. These results suggest that phospholipase C is probably not activated. The formation of lysophosphatidylinositol was also stimulated by thrombin and ionophore A23187, both activators of prostaglandin synthesis. Dexamethasone, a lipase inhibitor, inhibited the appearance of lysophosphatidylinositol, whereas aspirin and low concentrations of indomethacin, the cyclooxygenase inhibitor, did not inhibit. The results presented in ths paper provide evidence that a phospholipase A2-hydrolyzing phosphatidylinositol is activated when intact cells are stimulated for prostaglandin synthesis.

Animals↗
PubMed1980

Tranylcypromine and 15-hydroperoxyarachidonate affect arachidonic acid release in addition to inhibition of prostacyclin synthesis in calf aortic endothelial cells.

In this paper, we examined the effect of two known inhibitors of prostacyclin synthetase, tranylcypromine and 15-hydroperoxyarachidonate, on bradykinin-stimulated prostacyclin synthesis and arachidonic acid release from cellular phospholipids in endothelial cells derived from calf aorta. These two inhibitors inhibit prostacyclin synthesis stimulated by bradykinin, arachidonic acid, and ionophore A23187. However, these two inhibitors also affect the release of arachidonic acid from cells. Using cells prelabeled with [3H]arachidonic acid, we found that bradykinin-stimulated arachidonic acid release is severely inhibited by tranylcypromine (500 microgram/ml) but is stimulated by 15-hydroxyperoxyarachidonate at a concentration as low as 1 microgram/ml. We also found that 15-hydroperoxyarachidonate inhibits not only prostacyclin formation but also prostaglandin formation from the released arachidonic acid. Under the conditions used, these two compounds have no effects on the cell viability as judged by trypan blue exclusion test. We conclude that tranylcypromine and 15-hydroperoxyarachidonate not only inhibit prostacyclin synthesis but also affect other steps in the metabolism of arachidonic acid in whole cells.

Animals↗
PubMed1979

Specificity of phospholipases in methylcholanthrene-transformed mouse fibroblasts activated by bradykinin, thrombin, serum, and ionophore A23187.

Methylcholanthrene-transformed mouse fibroblasts synthesize prostaglandins in response to bradykinin, thrombin, serum, and the ionophore A23187. These agents activate phospholipases, thereby releasing fatty acids from phospholipids. To examine the phospholipid specificity of the phospholipases activated by bradykinin, thrombin, serum, and A23187, cells were labeled with [14C]arachidonic acid and stimulated with these agents in the presence of delipidated bovine serum albumin. Phospholipid classes were resolved by two-dimensional chromatography on silica gel-coated paper. Only phosphatidylinositol and phosphatidylcholine lost radioactivity upon stimulation. To characterize the fatty acid specificity of the phospholipases, cells were incubated with 14C-labeled stearic, oleic, linoleic, eicosatrienoic, or arachidonic acid and then exposed to the stimuli. Bradykinin, thrombin, and serum caused specific release of radioactivity into the medium only from cells labeled with arachidonic acid or eicosatrienoic acid, whereas A23187 caused release from cells labeled with any one of the five fatty acids. We conclude that bradykinin, thrombin, and serum activate phospholipases that specifically hydrolyze arachidonyl and eicosatrienoyl phosphatidylinositol and phosphatidylcholine, whereas A23187 is less specific activator of phospholipases.

Animals↗
PubMed1979

Arachidonic acid level in cellular lipids determines the amount of prostaglandins synthesized during cell growth in tissue culture.

Methylcholanthrene transformed mouse fibroblast cells can be induced to synthesize prostaglandins by a short term incubation with various vasoactive agents including serum, bradykinin and thrombin or in response to mechanical detachment from the culture dish. The ability of the cells to synthesize prostaglandins upon stimulation changes during growth of the culture on the dish; the response is maximal on the first day after inoculation and decreased sharply thereafter. Feeding of the cells with fresh growth medium enhances prostaglandin production induced by all stimuli. The difference in the cell response during growth is probably not due to change of prostaglandin synthetase activity since the specific enzyme activities assayed with microsomal preparations of cells harvested from the first and third day culture are similar. However, analysis of the cellular content of arachidonic acid after saponification of the total lipid extract of cells harvested at different days of growth reveals that the level of arachidonic acid per cell during growth is parallel to the response to stimuli. It is maximal on the first day and decreases sharply on the second day and stays low on the third day. Our study suggests that the level of arachidonic acid in the cell governs the extent of prostaglandin synthesis upon stimulation.

Animals↗
PubMed1977

Prostaglandin production by methylcholanthrene-transformed mouse BALB/3T3. Requirement for protein synthesis.

Stimulation of prostaglandin synthesis in transformed mouse fibroblasts by serum, thrombin, and bradykinin was blocked by actinomycin D and cycloheximide. These RNA and protein synthesis inhibitors did not affect prostaglandin synthetase in vitro or in vivo; nor did they affect the acylation of arachidonic acid into phospholipids. Serum-stimulated release of arachidonic acid and prostaglandins from [3H]arachidonic acid-labeled cells also was inhibited by actinomycin D and cycloheximide. RNA and protein synthesis appear to be required for expression of phospholipase activity; a prerequisite for prostaglandin synthesis by these cells.

Animals↗
PubMed1977

Elevated prostaglandins synthetase activity in methylcholanthrene-transformed mouse BALB/3T3.

Cell lines transformed from 3T3 spontaneously, by radiation, or by treatment with chemical carcinogens, polyoma and SV40 virus produce up to 5 times more prostaglandins than their untransformed parent line. Several aspects of prostaglandin biosynthesis by MC5-5 and 3T3 were compared. When stimulated by serum, bradykinin, or thrombin, MC5-5 cells labeled with radioactive arachidonic acid in their cellular lipids, these higher levels were shown not to be due to increased availability of the prostaglandin precursor, arachidonic acid. Prostaglandin synthetase activity in microsomal fractions prepared from MC5-5 was 6 times higher than that of microsomes of untransformed cells. The increased prostaglandin levels produced by transformed cells therefore appear to be the result of elevated prostaglandin synthetase activity.

Animals↗
PubMed1977

Analogues of anthracene, phenanthrene, and benzoflavone inhibit prostaglandin biosynthesis by cells in culture.

Prostaglandin production by methylcholanthrene-transformed 3T3 mouse fibroblasts (MC5-5), human normal fibroblasts (D550), and canine kidney (MDCK) cells was inhibited by several analogues of anthracene, phenanthrene, and benzoflavone. Among the most effective inhibitors of MC5-5's prostaglandin production were anthracene (ID50=1.7 micrometer), 9,10-diaminophenanthrene (ID50=0.48 micrometer), and 7,8-benzoflavone (ID50=0.55 micrometer). Under identical conditions, the ID50's for indomethacin and aspirin were 0.049 and 8.9 micrometer respectively. Production of radioactive prostaglandins by MC5-5 cells from tritiated phospholipids was blocked by 7,8-benzoflavone, but not the release of radioactive arachidonic acid.

Animals↗
PubMed1976

Stimulation of prostaglandin synthesis by bradykinin and thrombin and their mechanisms of action on MC5-5 fibroblasts.

Transformed mouse fibroblasts, in which [3H]arachidonic acid was incorporated in the cellular lipids, released radioactive materials into the medium when stimulated by bradykinin and thrombin. Most of this released radioactivity was found in the landins; the remainder was present in the arachidonic acid fraction. When the cells stimulated by serum or when they were mechanically manipulated, not only prostaglandins but also high levels of arachidonic acid were released. Anti-inflammatory steroids, which decrease the availability of arachidonic acid, inhibited the stimulated release of prostaglandins caused by the vasoactive agents, suggesting that bradykinin and thrombin stimulated prostaglandin synthesis by increasing deacylation of the phospholipids. The efficiency of the conversion of the released arachidonic acid into prostaglandins appears to reflect the cellular proximity of the phospholipid deacylating activity and prostaglandin synthesizing system.

Arachidonic Acids↗
PubMed1976

Stimulation of prostaglandin biosynthesis by vasoactive substances in methylcholanthrene-transformed mouse BALB/3T3.

Prostaglandins E2 and F2alpha are present in the culture medium of methylcholanthrene-transformed mouse BALB/3T3 cells. The production of these prostaglandins is stimulated when the cells are incubated in the presence of serum, arachidonic acid, thrombin, and bradykinin, or if they are mechanically manipulated. Whereas the appearance of prostaglandins resulting from the latter four treatments is complete in several minutes, in the presence of serum the prostaglandin levels are still increasing ever after 2 hours. Stimulation by all of these treatments is additive. Indomethacin inhibits these stimulations, suggesting that the production of prostaglandins results from de novo biosynthesis.

Animals↗
PubMed1976

Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids.

Serum stimulates the production of prostaglandins by transformed mouse fibroblasts. Hydrocortisone (cortisol) inhibits this stimulation. The half-maximal inhibition occurs at 6x10-9 M. Studies with cells labeled with [3H]arachidonic acid in their lipids show that the stimulation by serum results in the release of arachidonic acid from the cellular lipids, mostly phospholipids. Hydrocrotisone inhibits this release but does not inhibit the production of prostaglandins from exogenously supplied arachidonic acid. This inhibition of arachidonic acid release from phospholipids may be the mechanism for the anti-inflammatory action of corticosteroids.

Administration, Topical↗