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Biomedical subjects

G Friedman

Publications and source records attributed to G Friedman.

At least 127 records · Page 7Linked to original sources
PubMed1986

Isolation and characterization of the apolipoprotein E receptor from canine and human liver.

Previous results have demonstrated that liver membranes possess two distinct lipoprotein receptors: a low density lipoprotein (LDL) receptor that binds lipoproteins containing either apolipoprotein (apo-) B or apo-E, and an apo-E-specific receptor that binds apo-E-containing lipoproteins, but not the apo-B-containing LDL. This study reports the isolation and purification of apo-B,E(LDL) and apo-E receptors from canine and human liver membranes. The receptors were solubilized with the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate and were partially purified by DEAE-cellulose chromatography. The apo-B,E(LDL) receptor was isolated by affinity chromatography on LDL-Sepharose. The apo-E receptor, which did not bind to the LDL-Sepharose column, was then purified by using an HDLc (cholesterol-induced high density lipoprotein)-Sepharose affinity column and an immunoaffinity column. Characterization of the receptors revealed that the hepatic apo-B,E(LDL) receptor is similar to the extrahepatic LDL receptor with an apparent Mr = 130,000 on non-reducing sodium dodecyl sulfate-polyacrylamide gels. The apo-E receptor was found to be distinct from the apo-B,E(LDL) receptor, with an apparent Mr = 56,000. The purified apo-E receptor displayed Ca2+-dependent binding to apo-E-containing lipoproteins and did not bind to LDL or chemically modified apo-E HDLc. Antibodies raised against the apo-B,E(LDL) receptor cross-reacted with the apo-E receptor. However, an antibody prepared against the apo-E receptor did not react with the apo-B,E(LDL) receptor. The apo-E receptor also differed from the apo-B,E(LDL) receptor in amino acid composition, indicating that the apo-E receptor and the apo-B,E(LDL) receptor are two distinct proteins. Immunoblot characterization with anti-apo-E receptor immunoglobulin G indicated that the apo-E receptor is present in the hepatic membranes of man, dogs, rats, and mice and is localized to the rat liver parenchymal cells.

Amino Acids↗
PubMed1986

Characterization of the lipoprotein lipase in the functional pool of rat heart by immunoblotting.

Rat hearts were perfused with heparin for 2 min at 4 degrees C. The lipoprotein lipase activity in the perfusate was inhibited by antiserum to rat adipose tissue lipoprotein lipase. By immunoblotting, the lipoprotein lipase derived from the functional pool of the heart was found to be a protein with an apparent Mr of 69 000. After incubation of the perfusate at 37 degrees C for 24 h an immunologically reactive protein with an apparent Mr of 28 000 was found. This protein is not a physiological derivative of the enzyme but a degradation product.

Animals↗
PubMed1986

Analysis of risk factors in 532 survivors of first myocardial infarction hospitalized in Jerusalem.

During the period January 1979-March 1983, we have conducted in Jerusalem a case control study of all patients under the age of 65 surviving their first diagnosed myocardial infarction, in order to evaluate the importance of the conventional risk factors and to detect additional factors through quantifying plasma apolipoprotein concentrations. As a control group, we have chosen a sample from a previously studied Jewish population (LRC study), representative of the adult Jerusalemite population, parents of children born during 1958-1961. To complete the younger age group missing in the LRC population, we added a population studied in the Kiryat Yovel district of Jerusalem. We report here the results obtained from interviews and analysis of 532 cases (448 males and 84 females), and 869 controls (457 males and 412 females). In order to overcome the effects of age and ethnic origin on the risk factors, we have divided our populations according to age and country of origin of their fathers. Age, sex, smoking, history of high blood pressure, diabetes, elevated plasma triglycerides and/or cholesterol, and decrease in plasma HDL cholesterol, emerged as the most powerful and significant risk factors in this study. Other putative risk factors such as socioeconomic status, dietary habits, physical activity and obesity index were not found to be significantly different between cases and controls. It is noteworthy that smoking was more important as a risk factor in the younger age groups, whereas hypertension and diabetes were more important in the older age groups, particularly in females. The differences in lipid levels were considerably more prominent in the young age groups in both sexes. Myocardial infarction was observed more frequently in patients of European or American extractions. Apolipoproteins A-I, A-II, E and B determined in this study were shown to be affected partly by age and country of origin. Apo E and apo B levels were significantly higher and Apo A-I significantly lower in patients with myocardial infarction when compared to controls.

Aged↗
PubMed1986

The sensation of facial swelling in temporal arteritis: a predictor for the development of visual disturbance.

The sensation of facial swelling in temporal arteritis may be an important predictor of the development of visual disturbance. A clinical report of two patients who developed a sensation of puffiness of the face without altered facial appearance, as a presenting symptom of temporal arteritis with visual disturbance is presented. This symptom, though documented previously by us, has not been identified before as a predictor of visual disturbance.

Aged↗
PubMed1985

Endogenous plasma lipoprotein lipase activity in fed and fasting rats may reflect the functional pool of endothelial lipoprotein lipase.

In this study, a correlation was sought between the circulating lipoprotein lipase activity and nutritional state in the rat. In fed rats, the plasma lipoprotein lipase activity was between 30 and 120 munits/ml, whereas after an overnight fast in restraining cages, the lipoprotein lipase plasma levels were between 280 and 500 munits/ml. The plasma lipoprotein lipase activity was inhibited by a specific high titre goat antiserum to rat lipoprotein lipase. No effect of fasting was seen on the plasma hepatic triacylglycerol lipase. 6 h after fasting, adipose tissue lipoprotein lipase decreased maximally, but plasma lipoprotein lipase was not changed and rose only after 16 h. Thus, it seems that most of the lipoprotein lipase activity in the fasting plasma was related to the 3-fold rise in lipoprotein lipase activity in the heart, which may represent total muscle lipoprotein lipase. The increase in heart lipoprotein lipase was due in part to an increase in the t1/2 of the enzyme from 1.2 to 2.9 h. To determine whether the high plasma levels in the fasting rats might result from impaired clearance of the enzyme by the liver, functional hepatectomy was carried out. 15 min after hepatectomy, plasma lipoprotein lipase rose up to 20-fold in fed and about 6-fold in fasting rats. Lipoprotein lipase activity extracted by the liver was calculated to be 30-60 munits/ml in the fed and 171-247 munits/ml plasma per min in fasting rats. An increase in lipoprotein lipase activity in extrahepatic tissues (heart, lung, kidney, diaphragm and adrenal) occurred 30 min after hepatectomy in fed rats. The increase in heart lipoprotein lipase was due to an increase in heparin-releasable fraction. Since no impairment of hepatic clearance of circulating plasma lipoprotein lipase was found, the high fasting plasma lipoprotein lipase activity may be related to an increase in enzyme synthesis, decreased enzyme turnover and an expansion of the functional pool in tissues such as the heart and probably muscle. The present findings indicate that measurement of endogenous plasma lipoprotein lipase can provide information with respect to the size of the functional pool under normal and pathological conditions.

Animals↗
PubMed1985

Importance of the different steps of glycosylation for the activity and secretion of lipoprotein lipase in rat preadipocytes studied with monensin and tunicamycin.

Lipoprotein lipase synthesized by cultured rat preadipocytes is present in three compartments: an intracellular, a surface-related 3-min heparin-releasable, and that secreted into the culture medium. 30 min after addition of 6 microM monensin, the lipoprotein lipase activity in the heparin-releasable compartment starts to decrease; by 4 h of monensin treatment the lipoprotein lipase activity in the heparin-releasable pool and in the culture medium is about 10% of that found in control dishes. The intracellular activity, which had been identified as lipoprotein lipase by an antiserum to lipoprotein lipase, increases slowly and doubles by 24 h. However, since the cellular compartment accounts for 10-25% of total activity, this increase does not account for the missing enzyme activity. To determine whether this enzyme molecule is synthesized but is not active, incorporation of labeled leucine, mannose and galactose into immunoadsorbable lipoprotein lipase was studied in control, monensin- or tunicamycin-treated cells. Addition of tunicamycin (5 micrograms/ml) for 24 h caused a 30-50% reduction in immunoadsorbable lipoprotein lipase, but the enzyme activity was reduced by 90%. On the other hand, 4 h monensin treatment reduced both incorporation of [3H]leucine into immunoadsorbable lipoprotein lipase and heparin-releasable and medium lipoprotein lipase activity by 57 to 77%. The immunoadsorbable lipoprotein lipase in the intracellular compartment has a [14C]mannose to [3H]galactose ratio of 0.15 and this ratio increased 6-fold in monensin-treated cells. The intracellular lipoprotein lipase in monensin-treated cells had the same affinity for both the native and synthetic substrate as the lipoprotein lipase in control cells, yet its spontaneous secretion into the culture medium and its release by 3 min heparin treatment was markedly decreased. The present results indicate that: the presence of asparagine-linked oligosaccharide (formation of which is inhibited by tunicamycin) is mandatory for the expression of lipoprotein lipase activity; lipoprotein lipase is active also in a high mannose form; and terminal glycosylation and oligosaccharide processing, which is inhibited by monensin, may be important for the appearance of heparin-releasable lipoprotein lipase and secretion of lipoprotein lipase into the medium.

Adipose Tissue↗
PubMed1985

The relationship of clinical status and therapeutic modality to natural killer cell activity in human breast cancer.

The role of clinical status and therapeutic intervention on natural cell-mediated cytotoxicity in breast cancer was ascertained by monitoring natural killer (NK) cell activity in peripheral blood samples. Patients with localized disease on chemotherapy showed significant reductions in NK activity concomitant with reduced lymphocyte numbers, when compared to untreated patients (18.1% versus 32.7%, P less than 0.005). Lymphocyte counts were included in a calculation of the absolute proportion of NK activity that incorporates a correction factor for the leukopenia that occurs as a result of cytotoxic therapy and disease progression. This calculation more accurately reflects the significant reduction of NK activity that occurs in patients with localized and systemic disease on chemotherapy when compared to untreated patients with no current evidence of disease (10.3% and 14.9% versus 30.7%, respectively; P less than 0.001). Different chemotherapeutic regimens were found to selectively affect NK cell function. The levels of both actual and absolute NK activity were significantly reduced in patients receiving 5-fluorouracil and L-phenylalanine mustard; cyclophosphamide, methotrexate, and 5-fluorouracil; and vincristine, Adriamycin (doxorubicin), and 5-fluorouracil, whereas only the levels of absolute NK activity were significantly reduced in patients receiving mitomycin, Megace (megestrol acetate), and Adriamycin when compared to untreated cancer patients. In contrast, tamoxifen-treated patients demonstrated levels of actual and absolute NK activity observed with untreated cancer patients. Patients receiving tamoxifen showed significantly elevated NK activity when compared to patients on all other chemotherapies. These results indicate that monitoring NK cell function may be useful in assessing the immunosuppressive effects of chemotherapeutic intervention.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Echocardiographic findings after tricuspid valvectomy.

Resection of the tricuspid valve without prosthetic replacement has successfully been performed in patients with tricuspid valvular endocarditis. Using M-mode, two-dimensional, and Doppler echocardiograms, we studied four patients who underwent tricuspid valvectomy. All patients had previous history of intravenous drug abuse and staphylococcal endocarditis with tricuspid valvular involvement. In all patients, M-mode and two-dimensional echocardiograms showed that the tricuspid valve was absent. The right ventricle was dilated, and the interventricular septum had paradoxical motion in each patient. In each patient the right atrium was dilated, and with each ventricular systole, it expanded and its short axis increased by 20 to 33 percent. This caused shift of the interatrial septum toward the left atrium, with compression of its cavity. Doppler echocardiographic studies showed retrograde flow during systole in the right atrium, inferior vena cava, and hepatic vein. Echocardiographic findings in patients with tricuspid valvectomy correlate with the pathophysiologic findings of this condition.

Adult↗
PubMed1983

Modulation of lipoprotein lipase activity in cultured rat mesenchymal heart cells and preadipocytes by dibutyryl cyclic AMP, cholera toxin and 3-isobutyl-1-methylxanthine.

We have compared the effects of cellular cyclic AMP modulation on the regulation of lipoprotein lipase in cultures of rat epididymal pad preadipocytes and mesenchymal heart cells. Addition of dibutyryl cyclic AMP (dibutyryl cAMP) or 3-isobutyl-1-methylxanthine (IBMX) to preadipocytes grown in serum-containing culture medium resulted in a progressive decrease in lipoprotein lipase activity released into the culture medium so that at 6-8 h enzyme activity ranged between 20 and 30% of that recovered in the control dishes. Similar short-term (6-8 h) studies of the heart cell cultures showed a variable and much less pronounced depression of lipoprotein lipase activity. Thus, following dibutyryl cAMP and IBMX treatment, lipoprotein lipase activity ranged between 70 and 95% of control values. Incubation for 6 h with cholera toxin was followed by a 4-fold rise in the concentration of cellular cyclic AMP in both types of culture, but while in heart cell cultures enzyme activity was unchanged, lipoprotein lipase activity in preadipocytes decreased to 30% of control value. After 24 h incubation with all three effectors, an increase in lipoprotein lipase activity was seen. In the preadipocytes the increase ranged between 50 and 150% above control value, in the heart cell cultures it was 100-250%. 24-h incubation of heart cell cultures with dibutyryl cAMP resulted in a 6-fold increase of heparin-releasable lipoprotein lipase activity while residual activity was doubled. The rise in surface-bound lipoprotein lipase was evidenced also by an increase in the lipolysis of chylomicron triacylglycerol. In the presence of cycloheximide, the dibutyryl cAMP-induced heparin-releasable and residual lipoprotein lipase activity declined at the same rate as the basal activity. The reason for the difference in response of cultured preadipocytes and heart cells to the effectors during the first 8 h of incubation has not been elucidated, but could be related to a possible absence of hormone-sensitive lipase in the heart cells, and hence in a difference in intracellular metabolism of triacylglycerol. On the other hand, a common mechanism can be postulated for the long-term effect of cyclic AMP on the induction of lipoprotein lipase activity in both types of cultures. It probably involves mRNA and protein synthesis, which culminates in an increase in enzyme activity.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Lipoprotein lipase activity in cultured macrophage cell line J774(2) and its increase in variants deficient in adenylate cyclase and cyclic AMP-dependent protein kinase.

Three macrophage cell lines, J774(2), CT2 and J7H1 were compared with respect to synthesis and secretion of lipoprotein lipase. The enzyme activity measured was characterized as lipoprotein lipase on the basis of serum dependence and inhibition by 1 M NaCl. Enzyme activity in all three lines increased with time in culture and the highest activity was found in the medium of the CT2 line which is adenylate cyclase deficient while that in the J7H1 line, cyclic AMP-dependent protein kinase deficient, was intermediate. The half life of the enzyme activity in conditioned medium from all three lines was 30-40 min, suggesting that the different levels of activity observed do represent different levels of enzyme production by the cells. About 80% of the lipoprotein lipase activity from all three lines was present in the medium and 50-70% of cellular activity could be released into the medium by a 3-min exposure to heparin. In addition, 24 h incubation with heparin enhanced enzyme secretion in all three lines. To determine the role of cyclic AMP in the regulation of lipoprotein lipase activity use was made of dibutyryl cAMP, methyl isobutylxanthine (IBMX) and cholera toxin. These agents strikingly depressed lipoprotein lipase activity in the J774(2) line but only dibutyryl cAMP was active in the CT2 line (adenylate cyclase deficient). In the J7H1 (protein kinase deficient) line there was no response to dibutyryl cAMP or IBMX over the first 4 h of incubation. Addition of these agents did not affect total cell protein synthesis. The present findings indicate that in the intact cells changes in cyclic AMP levels are associated with a change in the activity of lipoprotein lipase.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Transfer of cholesteryl linoleyl ether from phosphatidylcholine and phosphatidylethanolamine liposomes to cultured cells catalyzed by lipoprotein lipase.

Unilamellar liposomes prepared from purified phospholipids (phosphatidylcholine, phosphatidylethanolamine or sphingomyelin) and labeled cholesteryl linoleyl ether were used to study lipoprotein lipase-catalyzed transfer of cholesteryl ester into cells in culture. In mesenchymal rat heart cell cultures, the transfer of cholesteryl linoleyl ether and cholesteryl linoleate was similar and related to the activity of endogenously produced lipoprotein lipase. In human skin fibroblasts transfer of labeled cholesteryl linoleyl ether was proportional to the concentration of milk lipoprotein lipase added to the incubation medium. Liposomes prepared from phosphatidylcholine or phosphatidylethanolamine were much better donors of cholesteryl ether to normal and apolipoprotein E-B receptor-negative fibroblasts and to endothelial cells than those prepared from sphingomyelin. Lysophosphatidylcholine was formed during incubation with milk lipoprotein lipase but was not considered to be directly responsible for the lipoprotein lipase-catalyzed transfer of cholesteryl ether. This conclusion was drawn because in the absence of lipoprotein lipase addition of lysophosphatidylcholine to liposomes, or almost complete phospholipolysis by phospholipase A2, did not result in the transfer of cholesteryl linoleyl ether from liposomes to cells. Attachment of lipoprotein lipase to the cell surface was mandatory for the transfer of cholesteryl ether and could be prevented by heparin. High density apolipoprotein reduced also the transfer of cholesteryl linoleyl ether, even though it did not interfere with the binding of labeled milk lipoprotein lipase to cultured fibroblasts. The present results provide evidence that lipoprotein lipase, and not the products of phospholipid hydrolysis, is the ligand for the non-apolipoprotein E-B receptor-mediated transfer of cholesteryl ester to cells.

Animals↗