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Biomedical subjects

A Chait

Publications and source records attributed to A Chait.

At least 127 records · Page 7Linked to original sources
PubMed1985

The effect of concanavalin A-stimulated mononuclear cells on low density lipoprotein receptor activity of cultured fibroblasts.

Secretory products of freshly isolated human circulating blood cells such as platelets, monocytes, and B lymphocytes, but not T lymphocytes, have previously been shown to enhance low density lipoprotein (LDL) metabolism by arterial wall cells. This study was undertaken to evaluate how secretory factor(s) from mononuclear cells that had been stimulated by concanavalin A (Con A) alters LDL receptor activity by cultured human skin fibroblasts. Conditioned medium from Con A-stimulated mononuclear cells produced an increase of 125I-LDL degradation accompanied by increased thymidine incorporation into DNA. The effect of conditioned medium from the Con A-stimulated mononuclear cells was mediated by the LDL receptor pathway. Degradation of HDL and methylated LDL, neither of which is taken up by the classical LDL receptor pathway, was not affected. The conditioned medium from these Con A-stimulated cells also failed to stimulate fluid pinocytosis, as measured by the uptake of [14C]sucrose. Some strains of fibroblasts, deficient in LDL receptors, responded to the conditioned medium from the Con A-stimulated mononuclear cells by increasing the very small amounts of LDL degraded by these cells. Fibroblasts from other homozygous familial hypercholesterolemic cell strains were unresponsive, however. The effect on LDL receptors was characterized by an increase in LDL receptor number without a change in the affinity of LDL for its receptor. Thus stimulated mononuclear cells secrete mitogens that also stimulate LDL receptor activity in human skin fibroblasts.

B-Lymphocytes↗
PubMed1985

Hyperlipidemia: forestalling complications in older diabetics.

Mild to moderate hypertriglyceridemia is not associated with specific signs or symptoms in either IDDM or NIDDM. However, symptoms of the "chylomicronemia syndrome," including abdominal pain and acute pancreatitis, can occur when poorly controlled diabetes is present in a patient with a familial form of hyperlipidemia. The low-carbohydrate, high-fat diet that was commonly recommended for diabetics during past years may have contributed to the elevated plasma LDL levels in some individuals. Such "diabetic diets" may also have played a role in the predisposition of diabetics toward atherosclerotic complications.

Arteriosclerosis↗
PubMed1985

Current status of renal angiography.

It is apparent that while indications for renal angiography remain, they have significantly decreased and changed over the years, with angiography having largely been replaced by other imaging modalities. It is perhaps indicative of the current role of renal angiography that at the 1985 courses and meetings of both the Society of Cardiovascular Radiology and the Society of Uroradiology there was virtually no discussion of this modality except as applied to the study and therapy of renovascular hypertension. Angiography is no longer the only and frequently not the best method of establishing the need for renal tumor surgery; however, it may prove indispensable in planning that surgery. It is no longer felt to be productive to use angiography in the differential diagnosis of chronic renal disease and renal failure or in the investigation of renal transplant rejection other than that related to anastomotic problems, despite the fact that the angiographic findings in these conditions have been well described. Magnetic resonance imaging shows early promise in this area of diagnosis. When angiography is performed, it is more often than not as a preliminary to an interventional, catheter-mediated procedure, rather than for a purely diagnostic purpose. As the efficient utilization of medical resources becomes of greater concern, the selection of the procedure most likely to be definitive from among the many imaging possibilities available in the genitourinary tract becomes a major responsibility of the treating physician and the radiologist in consultation. Both must be willing to adopt new and more efficient techniques as they become established, retaining older modalities in those situations in which the latter maintain superiority, at all times avoiding needless multiplicity of examinations.

Adrenal Gland Diseases↗
PubMed1984

Low-density lipoproteins modified by lipid transfer protein have altered biological activity.

Low-density lipoproteins (LDL) were modified by incubation with very-low-density lipoproteins (VLDL) and lipid transfer protein(s) to yield LDL particles that were enriched in triacylglycerol, depleted in cholesteryl esters, and contained apolipoprotein C. The uptake and degradation of these 125I-labeled modified LDL particles by cultured skin fibroblasts was reduced by approx. 30% when compared with LDL that had not been exposed to lipid transfer protein. Incubation of fibroblasts for 24 h in the presence of modified LDL resulted in less inhibition of LDL receptor activity and sterol synthesis than did incubation with control LDL. Both the degradation of 125I-labeled modified LDL and the effect of unlabeled modified LDL on the regulation of LDL binding and sterol synthesis were progressively decreased as the extent of modification of the LDL was increased. Even when identical amounts of modified LDL or control LDL protein were degraded, less inhibition of LDL receptor activity and sterol synthesis was observed with modified LDL than with control LDL, suggesting that the effects of modified LDL on these regulatory events are related to both the reduced degradation of the modified lipoprotein particles and to the alteration in its chemical composition. Uptake and degradation of modified LDL by human monocyte-derived macrophages in culture was reduced in a manner similar to that observed in the cultured fibroblasts, and was considerably less than that observed with acetylated LDL. No differences were observed between modified LDL prepared by exposure to lipid transfer activity in the lipoprotein deficient fraction of serum or when partially purified lipid transfer was used. Modified LDL, with similar composition to that used in the experiments, has been observed in certain diabetic and non-diabetic hypertriglyceridemic states. Thus, it is possible that the cellular metabolism of LDL in vivo might be altered in the presence of hypertriglyceridemia.

Acetates↗
PubMed1984

Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture.

Modification of low density lipoproteins by human arterial smooth muscle cells was characterized by increased electrophoretic mobility and increased content of malondialdehyde-like oxidation products reactive with thiobarbituric acid. Lipoprotein modification was promoted by micromolar concentrations of iron or copper in the culture medium and was metal ion concentration- and time-dependent. The ability of diverse media to promote smooth muscle cell-mediated low density lipoprotein modification correlated with their iron concentration. Therefore, metal ion concentration of culture media contributes substantially to low density lipoprotein modification in vitro. Human monocyte-derived macrophages took up and esterified the cholesterol from modified low density lipoprotein more extensively than from native low density lipoprotein. Metal ion-mediated modification of low density lipoprotein may be a contributing factor to the pathogenesis of arteriosclerosis.

Cells, Cultured↗
PubMed1984

In vivo stimulation of low-density lipoprotein degradation by insulin.

The effect of insulin on low-density lipoprotein (LDL) metabolism in vivo was evaluated using the euglycemic insulin clamp technique. In seven subjects, mononuclear cells isolated after a 4-h insulin infusion degraded more 125I-labeled LDL than cells isolated after a saline infusion in six control subjects. In addition, insulin caused the accelerated disappearance of 125I-labeled LDL from plasma in subjects previously injected with autologous 125I-LDL. Infusion of saline had no such effect. These data suggest that insulin, in vivo, stimulates LDL catabolism and could thereby influence LDL cholesterol levels. Insulin-induced stimulation of LDL catabolism could account for the reduction of LDL-cholesterol levels observed in intensively treated type I diabetic patients.

Adult↗
PubMed1983

Scavenger lipoprotein receptors are more effective in ligand internalization than low density lipoprotein receptors in human monocyte-macrophages.

Human monocyte-macrophages in culture express specific receptors for low density lipoproteins (LDL receptor) and human acetylated LDL (AcLDL receptors or scavenger receptors). After 24 h in lipoprotein-deficient serum, the cells expressed 2-3 fold more AcLDL receptors than LDL receptors as measured by trypsin releasable radioactivity after exposure to 125I-LDL or 125I-AcLDL at 37 degrees C. The efficiency of intracellular ligand delivery by the two receptors was evaluated as an internalization index (defined as intracellular + degraded/bound ligand). This index was several fold greater for 125I-AcLDL than for 125I-LDL, in the same cells exposed to either ligand under identical conditions. These results suggest that the scavenger receptors recycle more rapidly than do LDL receptors.

Cell Adhesion Molecules↗
PubMed1983

The effect of human T and B lymphocytes on low-density lipoprotein catabolism by cultured fibroblasts.

Freshly isolated human peripheral blood B lymphocytes degrade LDL via the LDL receptor pathway to a considerably greater extent than do freshly isolated T lymphocytes. In this study, B and T lymphocytes were compared for their ability to modulate LDL degradation in fibroblasts to which they were exposed. B and T lymphocytes were purified by sheep red blood cells rosette formation and passage through a nylon column. Lymphocytes and skin fibroblasts were co-cultured for 48 h in 10% lipoprotein-deficient serum before 125I-labeled LDL was added for measurement of its degradation. Co-culture with B lymphocytes increased LDL degradation by fibroblasts in a dose-dependent manner, but co-culture with T lymphocytes, did not. B lymphocytes had the same effects on human smooth muscle cells. The enhancement of LDL degradation in fibroblasts also was observed when fibroblasts were exposed to conditioned medium from B lymphocytes. The effects of B lymphocytes were not reproduced by exposure of fibroblasts to purified immunoglobulins or to B lymphocytes that had been freeze-thawed. These findings suggest that a secretory product of B lymphocytes can increase LDL receptor activity in other cells.

B-Lymphocytes↗
PubMed1983

Severe hypertriglyceridemia: role of familial and acquired disorders.

To evaluate the role of familial and secondary factors in the etiology of severe hypertriglyceridemia, family studies were performed and potential secondary causes of hypertriglyceridemia were evaluated in 54 patients with plasma triglyceride levels above 2000 mg/dl. Every subject had hypertriglyceridemic relatives, compatible with a familial form of hyperlipidemia, although plasma triglyceride levels in the relatives were substantially lower than in the index patients. In 5 index patients, both parents had hyperlipidemia. Four of these 5 had no coexisting secondary cause for hypertriglyceridemia. Forty-six of the remaining 49 (94%) also had potential secondary causes of hypertriglyceridemia, most commonly untreated diabetes mellitus. These findings suggest that severe hypertriglyceridemia frequently results from the coexistence of familial and secondary forms of hyperlipidemia.

Adolescent↗
PubMed1983

Human arterial wall cells secrete factors that are chemotactic for monocytes.

Macrophages and arterial smooth muscle cells comprise the cellular components of the atherosclerotic plaque. The vessel wall accumulation of macrophages occurs by a process of increased circulating monocyte migration into the vessel wall. In these studies it is demonstrated that human macrophages and arterial smooth muscle cells in culture secrete potent chemotactic factors for freshly isolated human monocytes. In contrast, human fibroblast-conditioned medium has no chemotactic activity. The effect of macrophage-conditioned medium is a function of macrophage differentiation and can be potentiated by macrophage activation. These results suggest that secretory products of human macrophages and arterial smooth muscle cells may be important stimuli for increased monocyte migration into the vessel wall in vivo.

Arteries↗
PubMed1983

Hydrocortisone decreases the internalization of low density lipoprotein in cultured human fibroblasts and arterial smooth muscle cells.

The effect of hydrocortisone on the cellular low density lipoprotein (LDL) pathway was studied in cultured human skin fibroblasts and arterial smooth muscle cells. Hydrocortisone decreased both uptake and degradation of 125I-LDL, LDL binding, measured at 4 C, was not affected by the hormone. Physiological concentrations of hydrocortisone (4 . 1 X 10(-8) mol/l) resulted in a 30% reduction of LDL uptake and degradation which could not be accounted for by an effect of the hormone on macromolecular synthesis, cell protein or cell number. To test whether the decrease in uptake and degradation of 125I-LDL was due to reduced internalization, the effect of hydrocortisone on the internalization of prebound LDL was determined and found to be decreased. Also, preincubation with unlabelled LDL in the presence of hydrocortisone resulted in less down regulation of LDL receptor activity than when no hydrocortisone was present. An effect of the hormone on bulk phase endocytosis has been excluded, since hydrocortisone did not affect either LDL degradation by receptor negative cells or endocytosis of 14C-sucrose by normal skin fibroblasts. Thus, hydrocortisone impairs LDL catabolism by decreasing the internalization of LDL normally bound to its cell surface receptor. These results may be relevant to the pathogenesis of atherosclerosis in conditions associated with reduced cellular LDL catabolism.

Aorta, Thoracic↗
PubMed1983

Human erythroleukemia cell line (HEL) undergoes a drastic macrophage-like shift with TPA.

We investigated the effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the human erythroleukemia cell line, HEL, and found that TPA addition (10(-6)-10(-8) M) to HEL cell cultures induces morphological, functional, and biochemical changes in HEL cells that are characteristic for macrophage-like cells. Apart from the drastic changes in morphology, the cells greatly enhance their phagocytic ability and acquire receptors for binding and degradation of chemically modified lipoproteins. At the biochemical level, a newly synthesized 85K glycoprotein is observed, and the cells are unresponsive to inducers of globin synthesis. Comparative observations with K562 cells indicate that TPA inhibits, as in HEL cells, spontaneous and induced globin synthesis, but induces minimal macrophage-like properties in these cells. The results with HEL cells are interpreted to indicate that TPA uncovers a latent monocyte-like phenotype in these cells.

Acid Phosphatase↗
PubMed1983

The role of lipoprotein receptors in lipid transport and in the pathogenesis of the hyperlipoproteinemias.

Three distinct classes of receptors for lipoproteins exist. The best studied is the LDL receptor, the primary function of which is the delivery of cholesterol in response to cellular needs. Although originally thought to be specific for LDL, it clearly recognizes lipoproteins that contain either apo B or E. It plays an important role in the catabolism of LDL and could also be involved in reverse cholesterol transport. The hepatic remnant receptor, a distinct binding site on liver membranes that recognizes apo E but not apo B, appears to function in the clearance of chylomicrons (and probably VLDL) remnants from the circulation, but also is likely to be important in the recognition of apo E-containing HDL, and hence is likely to participate in the reverse cholesterol transport. Finally, there is now evidence for a third group of lipoprotein receptors that are present on the cell surface of macrophages. They appear to bind lipoproteins that have been altered chemically or biologically and probably serve a scavenger function. While many of the model systems for studying these macrophage receptors have focused on chemical modifications that are unlikely to occur in vivo, several lipoproteins that have been shown to interact with these receptors may be naturally occurring or result from biological processes. The discovery of the three receptor classes has resulted in a dramatic increase in the understanding of lipoprotein physiology and pathophysiology, and future studies should further expand our understanding of the regulation of lipoprotein metabolism and its relationship to hyperlipoproteinemia and atherosclerosis.

Animals↗
PubMed1983

Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.

Plasma lipoprotein concentration, composition, and size were evaluated in two common familial forms of hypertriglyceridemia and compared with those in normal subjects. The very low density lipoproteins (VLDL) were triglyceride-enriched in familial hypertriglyceridemia (triglyceride/apoprotein B ratio: 25.7 +/- 8.9) as compared to normal (9.6 +/- 12.2, P < 0.001) or familial combined hyperlipidemia (9.7 +/- 3.3, P < 0.001). The diameter of VLDL was larger in familial hypertriglyceridemia (3.27 +/- 0.28 pm) than in familial combined hyperlipidemia (2.87 +/- 0.16 pm, P < 0.02). Although in familial hypertriglyceridemia VLDL tended to be larger, and in familial combined hyperlipidemia VLDL tended to be smaller than normal (3.08 +/- 0.48 pm), neither of these differences were significant. While VLDL was normally distributed in the control population, the size was skewed to larger particles in familial hypertriglyceridemia with fewer small particles (P < 0.05) and skewed to smaller particles in familial combined hyperlipidemia with fewer large particles (P < 0.05). VLDL was reciprocally related to low density lipoproteins (LDL) in familial combined hyperlipidemia (r = -0.80 to -0.87) suggesting that the concentrations of these individual lipoprotein groups were somehow interrelated. There was no significant relationship between these two lipoprotein classes in familial hypertriglyceridemia or in normals. In familial combined hyperlipidemia, the apoprotein A-I/A-II ratio was below normal (P < 0.01) suggestive of low HDL(2) levels. This change in apoprotein composition was independent of VLDL or LDL concentration. In familial hypertriglyceridemia, high density lipoprotein (HDL) cholesterol was reduced (33% below mean normal) and HDL triglyceride was increased (by 46%), while the concentration of apoA-I and apoA-II was normal. VLDL triglyceride was inversely related to HDL cholesterol in familial hypertriglyceridemia (r = -0.74, P < 0.005), but not in familial combined hyperlipidemia. The large, triglyceride-enriched VLDL observed in familial hypertriglyceridemia is compatible with the reported increase in VLDL triglyceride synthesis seen in this disorder. The increase in VLDL apoprotein B synthesis previously reported in familial combined hyperlipidemia was associated with VLDL of normal composition. The changes in HDL cholesterol in these two disorders might reflect exchange of triglyceride between VLDL and HDL or could be related to transfer of surface components during the catabolism of VLDL. The reciprocal relationship between various components of VLDL and LDL seen in familial combined hyperlipidemia, but not in familial hypertriglyceridemia or in normal subjects, might provide some insight into the pathological abnormalities in these disorders. The differences between these two common familial forms of hypertriglyceridemia provide further support that they are distinct entities.-Brunzell, J. D., J. J. Albers, A. Chait, S. M. Grundy, E. Groszek, and G. B. McDonald. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia.

Adult↗
PubMed1983

Aortoiliac arteriovenous fistula simulating iliac vein thrombosis following intervertebral disc surgery.

This report describes an unusual presentation of arteriovenous fistula secondary to intervertebral disc surgery. A 61-year-old obese woman underwent operation for a herniated intervertebral disc. One month later she was readmitted with painful swelling of the left calf. The condition progressed to include pigmentation of the whole extremity with varicosities and ulcerations. The femoral vein was found to be occluded and there were multiple collateral vessels in the thigh. Initially, phlebitis was diagnosed, then iliac vein thrombosis. Her symptoms improved slightly with rest and anticoagulant therapy. Finally, after 2 years, an arteriovenous fistula was suspected because of a bruit in the presacral region and oxygen saturation of venous blood in the thigh. The diagnosis was confirmed by aortography. The fistula was transected and the artery and vein individually sutured, producing immediate improvement. The patient was symptom-free 3 years later. When chronic venous obstruction, unusual distribution of collateral circulation and pigmentation of a lower extremity are found after disc surgery, an arteriovenous fistula should be suspected. The diagnostic procedures should include auscultation of the abdomen and back, venography, measurement of blood oxygen levels in the collateral venous circulation and aortography.

Aortic Diseases↗
PubMed1982

Low density lipoprotein receptor activity in freshly isolated human blood monocytes and lymphocytes.

Circulating human monocytes and lymphocytes were isolated by counterflow and density gradient centrifugation. Binding and degradation of low density lipoprotein (LDL) occurred predominantly in monocytes and to a much lesser extent in lymphocytes. The findings were consistent with greater LDL receptor activity in freshly isolated monocytes than lymphocytes, in keeping with differences in other cell surface receptors between these two cell types. Therefore, when freshly isolated mixed mononuclear cells are used to study LDL receptor activity in vivo in humans, careful attention needs to be given to the proportions of monocytes and lymphocytes, or alternatively, relatively pure preparations of monocytes should be used.

Cell Separation↗
PubMed1982

Lipoprotein lipase secretion by human monocyte-derived macrophages.

Human monocyte-derived macrophages in culture produced lipoprotein lipase. Although freshly isolated blood monocytes did not secrete much lipase activity, 1 d in culture was sufficient to trigger measureable enzyme production. During 3 wk in culture, maximal activity was attained after 7 d. At all times, the culture medium contained more enzyme activity than did a serum-heparin eluate or a detergent extract of the cell layer. The lipase activity was stimulated by serum and was inhibited by preincubation with antiserum to bovine lipoprotein lipase or when assayed at a high salt concentration. Furthermore, the enzyme bound to a heparin-Sepharose affinity column at physiological ionic strength. Cells cultured from a subject with primary lipoprotein lipase deficiency secreted no detectable enzyme. Since macrophages are prominent components of atherosclerotic lesions in man, their ability to synthesize and secrete lipoprotein lipase may be important to atherogenesis.

Adult↗