Interactions of plasma lipoproteins with endothelial cells.
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Animals↗
Biomedical subjects
E M Mahoney
Publications and source records attributed to E M Mahoney.
Nonenzymatic glucosylation of low-density lipoprotein alters its biologic activity.
Human low-density lipoprotein (LDL) was glucosylated by incubation in vitro with glucose (20-80 mM) with or without addition of cyanoborohydride. The incorporation of covalently bound glucose was linear over time, and amino acid analysis showed the presence of glucosyllysine residues. The glucosylated LDL (glc LDL) moved more rapidly than normal LDL on agarose electrophoresis. The rate of degradation of 125I-labeled glucosylated LDL (glc LDL) by cultured human fibroblasts was reduced compared with that of native I-LDL, the difference increasing with extent of glucosylation. Effects were seen with blockage of as few as 6-15% of the LDL lysine residues; high-affinity degradation was completely lost when one-third of the lysine residues were blocked. Conjugation of LDL with glucose-6-phosphate also blocked high-affinity uptake and degradation. Whereas native LDL uptake inhibited the activity of beta-hydroxy-beta-methylglutaryl coenzyme A reductase and stimulated acyl coenzyme A:cholesterol acyltransferase activity, glc LDL had no effects on these enzymes. The fractional catabolic rate of glc LDL in guinea pigs was reduced. Degradation of glc LDL by mouse peritoneal macrophages was not significantly faster than that of native LDL. Finally, the presence of glc LDL in human plasma was demonstrated. Preliminary data show that 1.3% of lysine residues in normal LDL and 2-5.3% of lysines in diabetic LDL were glucosylated. Since, like other plasma proteins, LDL undergoes glucosylation in diabetes, its turnover and sites of catabolism may differ from normal and this may be relevant to the accelerated atherosclerosis of diabetes.
Amino Acids↗
Neutral cholesterol esterase activity in macrophages and its enhancement by cAMP-dependent protein kinase.
Cholesterol esterase with optimal activity at pH 6.8 was found in the 40,000 X g supernatant fraction prepared from rabbit alveolar macrophages, thioglycolate-elicited mouse peritoneal macrophages, and the J774 macrophage cell line. The neutral cholesterol esterase activity in these three types of macrophages was of the same order of magnitude as that in the 40,000 X g supernatant fraction of adrenal, heart, and liver but considerably lower than that in adipose tissue. The enzyme prepared from J774 cells was activated about 60% by preincubation with cAMP and Mg-ATP; half-maximal activation was obtained at 2.5 X 10(-7) M cAmP. The activation was completely blocked by a specific protein inhibitor of cAMP-dependent protein kinase. These findings suggest that cytoplasmic cholesterol esters stored in macrophages can be mobilized for release by action of the neutral enzyme described and, further, that this process may be regulated by factors that affect intracellular cAMP levels.
Animals↗
Secretion of lipoprotein lipase by macrophages in culture.
Cultured macrophages were shown to synthesize and constitutively secrete a triglyceride lipase identified as lipoprotein lipase on the basis of the following criteria: 1) it required apolipoprotein C-II for optimal activity; 2) it exhibited maximal activity at pH 8.2; 3) it was inhibited by 1 M NaCl; 4) it bound tightly to a heparin-Sepharose affinity gel and was eluted with buffer containing 1.5 M NaCl; and 5) the quantity of enzyme released from macrophages was enhanced by heparin. Cycloheximide treatment of macrophage cultures blocked the spontaneous secretion of lipoprotein lipase. Macrophage secretion of lipoprotein lipase may be relevant to the role of this cell in atherogenesis.
Animals↗
Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins.
Human low density lipoprotein (LDL) was incubated with an established line of rabbit aortic endothelial cells. Density gradient fractionation showed a time-, concentration-, and temperature-dependent increase in the average density of the LDL (from about 1.036 to as high as 1.070 g/ml). Incubation without cells or with other types of cultured cells (fibroblasts, hepatocytes, 3T3-L1 cells) caused no significant change in density. 125I-Labeled LDL (125I-LDL) recovered after incubation with endothelial cells (EC-modified LDL) was taken up and degraded 3 to 4 times more rapidly than control LDL by resident mouse peritoneal macrophages and by an established tumor line of mouse macrophages (J774 cells). Macrophage degradation of EC-modified 125I-LDL exhibited saturation kinetics (greater than 85% inhibited by excess unlabeled EC-modified LDL). Degradation was also inhibited by unlabeled acetylated LDL and, conversely, unlabeled EC-modified LDL inhibited degradation of acetylated 125I-LDL. Incubation of LDL with conditioned medium-removed from endothelial cell cultures modified neither its density nor its rate of degradation by macrophages. These studies show that endothelial cells have the potential to metabolically modify the LDL molecule, generating a form that is more rapidly degraded by macrophages and that is recognized by the macrophage receptor for acetylated LDL. This process may play a significant role in the pathogenesis of atherosclerosis.
Animals↗
Influence of fatty acyl substitution on the composition and function of macrophage membranes.
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Acetates↗
DNA polymerases in parasitic protozoans differ from host enzymes.
Analysis of extracts of the bloodstream forms of Trypanosoma brucei showed that both DNA polymerase-alpha and DNA polymerase-beta activities were present. The detection of DNA polymerase-beta in T. brucei demonstrates the presence of this enzyme in unicellular organisms. DNA polymerase-beta is present also in Leishmania mexicana. The DNA polymerases in T. brucei are immunologically distinct from the host enzymes. The structural differences between the parasite and the host enzymes could be exploited for the development of agents to combat parasitic diseases.
Animals↗
Successful prevention of ileal conduit stomal stenosis: experience during a 12-year period.
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Constriction, Pathologic↗
Useful technique for long-term urinary drainage by inlying ureteral stent. Six-year experience.
Endoscopically placed inlying ureteral stents have proved useful in the conservative management of patients with ureteral obstruction, urinary fistula, and malignancy and have obviated the need for operative intervention. In high-risk symptomatic patients with widespread malignancy, internal urinary diversion offers the opportunity for an improved quality of life without the surgical risk or potential morbidity of supravesical diversion. Potential candidates for this simple, safe, and effective technique include: those with postsurgical obstruction and/or fistula, retroperitoneal fibrosis, metastatic carcinoma, congenital ureteropelvic junction obstruction, as well as those with reversible obstruction from lymphoma and carcinoma of the prostate who are undergoing radiotherapy and/or chemotherapy. The focus of this report is on the technique we have found successful in providing us with stents that fit our individual patients. Readily available fabricated graduated ureteral catheter can be cut and shaped to particular measurements unlike prefabricated catheters. Minimal preparation time is demanded, and there is no need for extensive stocking of various catheter sizes.
Adolescent↗
A descriptive study of the attitudes of psychiatrists toward the new role of the nurse therapist.
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Attitude of Health Personnel↗
Functioning and nonfunctioning cysts of the adrenal cortex and medulla.
Adrenal cysts are rare clinical and pathologic entities. The vast majority are minute in size, unilateral, and found in females at autopsy. They come to the physician's attention when they produce symptoms or are identified on x-ray studies. When symptomatic, they generally produce lumbar discomfort and gastrointestinal symptoms, and occasionally are palpable by abdominal examination. There is no significant agreement as to cause and pathogenesis of the disease. The most common histologic types are lymphangiomatous endothelial cysts, secondary to lymphangiectasis, and the fibrous wall or hemorrhagic pseudocysts. In many patients preoperative diagnosis is now possible with high quality nephrotomography, ultrasonography, and adrenal arteriography. The presence of a suprarenal mass with peripheral or laminar calcification strongly suggests the presence of an adrenal pseudocyst. Selective biochemical studies are mandatory to rule out the presence of an occult cystic pheochromocytoma, and adrenal cortical tumor. Adrenal cysts must be differentiated from all space-occupying lesions of the upper abdomen. Surgical exploration is recommended in almost all patients for accurate diagnosis and to rule out malignant disease or occult pheochromocytoma. The choice of the surgical approach should be planned to provide for safe and adequate exposure, depending on the size and location of the lesion. Careful dissection with preservation of the adjacent kidney, liver, and pancreas should be performed.
Adrenal Cortex↗
Malignant pheochromocytoma: clinical course and treatment.
We describe 7 patients with 16 malignant pheochromocytomas, with followup for 7 to 21 years. Five patients are free of disease at a mean of 13.5 years and 2 patients died of malignancy at 10 and 13 years. The 3 criteria believed important for a maximum tumor-free interval are: 1) adjunctive lymphadenectomy at the initial operation when 1 or more lymph nodes contain tumor, 2) close followup of all patients with pheochromocytoma by diagnostic biochemical assay for 15 years and 3) an aggressive excision of all single or multiple recurrent pheochromocytomas as soon as a biochemical diagnosis is established.
Adolescent↗
An improved non-intubated cutaneous ureterostomy technique for the normal and dilated ureter.
Cutaneous ureterostomy is a simple procedure to perform but is attended by high morbidity owing to recurring abscesses, strictures and stenosis of the stoma. An improved technique applied to the diversion of 4 normal renal units and 3 dilated ureters is described. We have not experienced the complications mentioned in previous studies and none of the patients has required ureteral intubation in this small series with a 3-year followup.
Adult↗
Response of endocytosis to altered fatty acyl composition of macrophage phospholipids.
Mouse peritoneal macrophages incubated in serumless medium containing a 19:0 or trans-18:1 fatty acid complexed to bovine serum albumin incorporate the exogenous fatty acid supplement into cellular phospholipids. Within 8 hr, 25% of the total phospholipid fatty acids are derived from the supplement, with cell viability remaining greater than 95%. The incorporation of either of these supplements increases the saturated/unsaturated fatty acid ratio in the phospholipids 2-fold over that of cells cultured in serum and effects striking changes in endocytic activities. The levels of both fluid-phase pinocytosis and receptor-mediated phagocytosis are decreased at all temperatures examined between 15 degrees and 37 degrees. The increased degree of saturation of cell phospholipids correlates with decreased endocytic rates for both processes and with increased activation energies (Eact) for phagocytosis. The Eact values for phagocytosis, which range from 54 to 90 kcal/mol, depend on the supplementation conditions used. Although the levels of pinocytosis are depressed, the Eact values for pinocytosis (17--25 kcal/mol) are not strikingly affected by saturated fatty acid enrichment. These observations suggest that the degree of lipid fluidity of macrophage membranes influences both phagocytosis and pinocytosis in macrophages.
Acetates↗
Radical nephrectomy, bench surgery and autotransplantation in the potentially malignant renal mass.
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Adult↗
Venacavography, corticosteroids and surgery in the management of idiopathic retroperitoneal fibrosis.
Four patients with idiopathic retroperitoneal fibrosis were found to have characteristic obstruction and anterior displacement of the lumbar vena cava. Varying degrees of venous collateral circulation were present, depending on the degree of vena caval compression. All 4 patients underwent ureterolysis to relieve the hydronephrosis and to confirm diagnosis by biopsy. Two patients were treated with corticosteroids postoperatively. Followup venacavography demonstrated improved filling and decrease in the collateral circulation in these 2 patients. Of the remaining 2 untreated patients 1 was lost to followup and the other revealed no change. Diagnosis of idiopathic retroperitoneal fibrosis can be made if characteristic changes are present on inferior venacavography and may provide an objective measure for following the basic disease process during medical treatment.
Adult↗