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Biomedical subjects

M Fainaru

Publications and source records attributed to M Fainaru.

At least 19 recordsLinked to original sources
PubMed1992

Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride-rich lipoproteins.

Triglyceride rich-lipoproteins induce triglyceride accumulation in macrophages, leading to foam cell formation. The correlation between cell triglyceride accumulation and lipoprotein lipase (LPL) secretion in murine macrophages and the role that LPL plays in the accumulation process were examined. LPL secretion is defined as the extracellular LPL activity that accumulates during a 4-hour incubation of treated and untreated cells in a bovine serum albumin-containing RPMI-1640 medium. LPL secretion was suppressed (up to 70%) in a dose- and time-dependent manner when J774.1 cells were incubated with chylomicrons, very low density lipoproteins, and intermediate density lipoproteins but not with low or high density lipoproteins from normolipidemic and hypertriglyceridemic subjects. Oleic acid both suppressed LPL secretion and invoked triglyceride accumulation. Suppression of LPL secretion preceded gross triglyceride accumulation, was reversible, and was not the result of a reduction in LPL mRNA. P388D1 cells neither secreted LPL nor accumulated triglyceride. Inhibition of LPL secretion by tunicamycin in both peritoneal macrophages and J774.1 cells prevented a hypertriglyceridemic very low density lipoprotein-induced triglyceride accumulation, an effect that was counteracted by addition of exogenous LPL. The results suggest that 1) extracellular hydrolysis of lipoprotein triglyceride is a major factor in inducing foam cell formation and 2) LPL secretion may be regulated by cell energy needs, and when these needs are exceeded, LPL secretion is suppressed.

Animals↗
PubMed1990

[Alcohol-related admissions in a community hospital].

We reviewed 150 alcoholic patients (1.3% of all admissions) hospitalized in this department during 1983-1987 and compared them with a random sample of 450 other patients in the department during the same period. In the alcoholic group were more males, an increased prevalence of those of Yemenite and Indian origin, and a higher rate of unemployed. The clinical presentation was heterogenous. In 26% of the chronic alcoholics no abnormality related to alcoholic injury was detected. The other patients in that group suffered from a variety of clinical problems related to alcohol. In 41% the immediate cause of admission was related to chronic alcoholism, and in others (31%) we observed alcohol-related pathology in addition to the main cause of hospitalization. We wish to increase awareness of the medical problems of chronic alcoholics encountered in a community hospital in order to promote quicker diagnosis, avoid unnecessary diagnostic procedures, and lead to better medical care.

Alcoholism↗
PubMed1990

Kinetics of peritoneal protein loss during CAPD: I. Different characteristics for low and high molecular weight proteins.

We studied the peritoneal protein loss in 13 patients during CAPD using 2 liters of 1.5% dextrose dialysis solutions. We compared the kinetic characteristics of the peritoneal mass transfer and clearance of proteins over a wide range of molecular size, to those of small molecular weight solutes. The peritoneal clearance of all studied proteins and solutes correlated strongly and negatively with their molecular mass. No changes were observed in these clearances during 58 months of dialysis. Unlike the peritoneal mass transfer and clearance of small molecular weight solutes (less than 200) which revealed a remarkable progressive drop after the first hour of an eight-hour dialysis cycle, the mass transfer and clearance of proteins of large molecular weight (greater than 68,000) was continuous throughout the eight hours. The clearance of proteins of small molecular weight (less than 15,000) showed similar kinetics to small solutes (less than 200). These results indicate that long dwell times (6 or 8 hr) of peritoneal dialysis are detrimental for the loss of large molecular weight proteins (such as albumin and immunoglobulins) in view of the negligible dialysance of both small solutes (creatinine and potassium) and "intermediate molecules" (represented by the small molecular weight proteins) during the latter hours of long dwell cycles. Thus we suggest that substituting CAPD (3 x 8 hr or 4 x 6 hr) with CCPD (6 x 1 hr) may limit protein loss in these patients.

Adult↗
PubMed1990

Kinetics of peritoneal protein loss during CAPD: II. Lipoprotein leakage and its impact on plasma lipid levels.

We quantified the plasma levels and peritoneal loss of lipids and lipoproteins, and studied the composition of plasma and effluent lipoproteins in 16 patients on CAPD (5 females and 11 males, 18 to 76 years old). Five patients were studied prospectively (at 0, 1, 3 and 6 months) and 11 patients at 6 to 58 months on CAPD (N = 30). Elevated levels of plasma VLDL and reduced levels of plasma HDL were maintained in these patients throughout 58 months of CAPD, whereas the initially increased LDL levels showed a tendency towards normalization. All plasma lipoproteins (VLDL, IDL, LDL and HDL) were present in the peritoneal effluent. The lipoproteins isolated from plasma and peritoneal fluid shared a similar lipid and apolipoprotein composition. The peritoneal transport characteristics of plasma lipoproteins were similar to other plasma macromolecules. Their clearance correlated with their molecular mass, plasma concentration and dwell time, but was not affected by duration of CAPD treatment. The plasma lipid and lipoprotein levels were unaffected by the rate of glucose absorption. The peritoneal protein clearance correlated positively with plasma levels of triglyceride and LDL, and negatively with plasma HDL. An inverse correlation was observed also between plasma levels of HDL and its peritoneal clearance (r = -0.393, P less than 0.025, N = 30). The continuous peritoneal loss of HDL and the hypertriglyceridemia were found to contribute most to the persistent low plasma levels of HDL in CAPD patients, and thus may lead to the accelerated atherosclerosis observed in these patients.

Adult↗
PubMed1990

Fish apolipoprotein-A-I has heparin binding activity: implication for nerve regeneration.

This study provides evidence that apolipoprotein-A-I (apo-A-I), derived from fish plasma and nerve, has heparin binding activity. We have shown previously that injury in a regenerative CNS, such as that of fish optic nerves, leads to increased levels of apo-A-I in media conditioned by these nerves, as compared with media conditioned by noninjured nerves. In the present study, we have purified and characterized apo-A-I from both fish plasma and optic nerves. Sequence analysis of the 15 N-terminal amino acids revealed that at least 14 amino acids are identical in these two purified apo-A-I samples. The purified apo-A-I derived from both fish plasma and optic nerves binds to heparin. Binding measurements using [3H]heparin followed by Scatchard analysis revealed that apo-A-I binds to heparin with relatively low affinity (KD = 2.8 x 10(-6) M). Results are discussed with respect to the possibility that accumulation of apo-A-I in the extracellular matrix of fish optic nerves is made possible via heparin binding, like that to apolipoprotein-E in mammals.

Amino Acid Sequence↗
PubMed1989

Chylomicron-chylomicron remnant clearance by liver and bone marrow in rabbits. Factors that modify tissue-specific uptake.

The metabolism of [14C]cholesterol- and [3H]retinol-labeled chylomicrons obtained from canine thoracic duct or rabbit mesenteric lymph was investigated in normal fasted rabbits. Typically, 70-80% of the chylomicrons injected into the rabbits were cleared from the plasma in 20 min, and their uptake was accounted for principally by the liver and the bone marrow. Surprisingly, the bone marrow was a major site of uptake; the uptake ranged from about half that of the liver to a nearly equal amount. The importance and specificity of chylomicron-chylomicron remnant uptake by the bone marrow were established by demonstrating that (a) bone marrow throughout the body accumulated these lipoproteins, (b) the level of uptake was consistent regardless of how the values were calculated or how the chylomicrons were prepared, (c) the uptake represented specific binding, and (d) radiolabeled intestinal lipoproteins induced in vivo delivered cholesterol and retinol to the marrow. Electron microscopic examination of the rabbit bone marrow established that perisinusoidal macrophages uniquely accounted for the uptake of the chylomicrons. Whereas liver cleared a variety of both triglyceride-rich lipoproteins (chylomicrons, chylomicron remnants, and very low density lipoproteins) and cholesterol-rich lipoproteins (beta-very low density lipoproteins and high density lipoproteins containing apolipoprotein E), bone marrow uptake appeared to be restricted to the triglyceride-rich lipoproteins. More chylomicron remnants (generated in a hepatectomized rabbit) were cleared by the liver than by the bone marrow, and the addition of excess apolipoprotein E to chylomicrons resulted in their preferential uptake by the liver. The role of chylomicron-chylomicron remnant delivery of lipids or lipid-soluble vitamins to rabbit bone marrow is open to speculation, and whether triglyceride-rich lipoprotein uptake occurs to a significant extent in the bone marrow of humans remains to be determined.

Animals↗
PubMed1989

Optic nerve regeneration in adult fish and apolipoprotein A-I.

Fish optic nerves, unlike mammalian optic nerves, are endowed with a high capacity to regenerate. Injury to fish optic nerves causes pronounced changes in the composition of pulse-labeled substances derived from the surrounding non-neuronal cells. The most prominent of these injury-induced changes is in a 28-kilodalton (kDa) polypeptide whose level increases after injury, as revealed by one-dimensional gel electrophoresis and autoradiography. The present study identified as apolipoprotein A-I (apo-A-I) a polypeptide of 28 kDa in media conditioned by regenerating fish optic nerves. The level of this polypeptide increased after injury by approximately 35%. Apo-A-I was isolated by gel-permeation chromatography from delipidated high-density lipoproteins (HDL) that had been obtained from carp plasma by sequential ultracentrifugation. Further identification of the purified protein as apo-A-I was based on its molecular mass (28 kDa) as determined by gel electrophoresis, amino acid composition, and microheterogeneity studies. The isolated protein was further analyzed by immunoblots of two-dimensional gels and was found to contain six isoforms. Western blot analysis using antibodies directed against the isolated plasma protein showed that the 28-kDa polypeptide in the preparation of soluble substances derived from the fish optic nerves (conditioned media, CM) cross-reacted immunologically with the isolated fish plasma apo-A-I. Immunoblots of two-dimensional gels revealed the presence of three apo-A-I isoforms in the CM of regenerating fish optic nerves (pIs: 6.49, 6.64, and 6.73). At least some of the apo-A-I found in the CM is derived from the nerve, as was shown by pulse labeling with [35S]methionine, followed by immunoprecipitation. The apo-A-I immunoactive polypeptides in the CM of the fish optic nerve were found in high molecular-weight, putative HDL-like particles. Immunocytochemical staining revealed that apo-A-I immunoreactive sites were present in the fish optic nerves. Higher labeling was found in injured nerves (between the site of injury and the brain) than in non-injured nerves. The accumulation of apo-A-I in nerves that are capable of regenerating may be similar to that of apo-E in sciatic nerves of mammals (a regenerative system); in contrast, although its synthesis is increased, apo-A-I does not accumulate in avian optic nerves nor does apo-E in rat optic nerves (two nonregenerative systems).

Animals↗
PubMed1989

Serum and effluent lysozyme (muramidase) activity in CAPD patients.

The elevated serum lysozyme activity in 13 chronic renal failure patients (n = 26) dropped significantly during their first three months of CAPD and subsequently returned to initial levels. When compared with peritoneal mass transfer of lysozyme and serum creatinine levels, a distinct correlation was observed between these and the fluctuations in serum lysozyme activity recorded up to three years of CAPD (r = 0.319, P less than 0.05 and r = 0.425, P less than 0.025, respectively). A notable drop in the mass transfer of this low molecular weight protein took place after the first hour of dialysis. We concluded that long-term CAPD does not affect serum lysozyme activity and that passive loss across the peritoneal membrane could account for the lysozyme found in the effluent fluid.

Adolescent↗
PubMed1988

Interactions between human and carp (Cyprimus carpio) low density lipoproteins (LDL) and LDL receptors.

1. We have compared the concentration and chemical composition of carp and human plasma lipoproteins and studied their interaction with human fibroblast LDL receptors. 2. The main lipoproteins in carp are of high density (HDL) in contrast to low density lipoproteins (LDL) in human. 3. Carp lipoproteins are devoid of apolipoprotein (apo) E, a major ligand for interaction with LDL receptors in mammals. 4. Carp very low density lipoproteins (VLDL) and LDL but not HDL nor apoA-I cross react with human LDL in their interaction with LDL receptors on human cultured fibroblasts. 5. Carp liver membranes possess high affinity receptors that are saturable and have calcium dependent ligand specificity (apoB and apoE) similar to human LDL receptor. Carp VLDL and LDL but not HDL nor its major apolipoprotein complexed to L-alpha-phosphatidylcholine dimyristoyl (apoA-I-DMPC) competed with the specific binding of human LDL to this receptor.

Adult↗
PubMed1988

Hypolipidemic effect of beta, beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) in normal and nephrotic rats.

Treatment of normal or puromycin aminonucleoside-nephrotic rats, kept on a balanced Purina chow diet, with beta, beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) (Bar-Tana, J., G. Rose-Kahn, and M. Srebnik. 1985. J. Biol. Chem. 260: 8404-8410) resulted in an acute reversible inhibition of liver lipogenesis and cholesterogenesis with a concomitant hypolipidemic effect which was sustained as long as the drug was administered. The hypolipidemic effect in normal and nephrotic rats consisted of 70-80% and 40-60% reduction in plasma VLDL-triacylglycerols and cholesterol, respectively, with a respective increase in the HDL-cholesterol/(VLDL + LDL)-cholesterol ratio. The observed hypolipidemic effect was accompanied by a 10-fold decrease in VLDL-apoC-III content with a concomitant enrichment of the VLDL fraction by VLDL remnants having an increased apoB-100/apoB-48 ratio. The pharmacological reduction of VLDL by MEDICA 16 may offer a treatment mode of choice for selected hyperlipidemic states.

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

Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy: studies in type IIA and type IIb hyperlipoproteinaemia.

The effects of lipid lowering therapy (bezafibrate) on plasma lipoproteins was investigated in twelve patients with familial hypercholesterolaemia (type IIA) and eight with familial combined hyperlipidaemia (type IIB). Bezafibrate caused a decrease of plasma cholesterol, plasma triglycerides, plasma apolipoprotein B, VLDL cholesterol and LDL cholesterol and an increase of HDL cholesterol. Post-heparin plasma lipoprotein and hepatic lipase activities increased in both groups (significant only in type IIB). Lipoprotein composition showed the following changes: Increased protein and phospholipids and decreased triglycerides and cholesteryl esters in VLDL. Decreased protein and triglycerides and increased free and esterified cholesterol in LDL. Decreased triglycerides and increased phospholipids in HDL. Cholesteryl ester to protein ratios decreased in VLDL and increased in LDL. The hydrated density of LDL (both groups) and of HDL3 (type IIB) decreased following bezafibrate therapy. These changes were in general similar to those observed in hypertriglyceridaemic patients and could be ascribed, at least in part, to the increase of plasma lipase activities and the decrease of lipid transfer reactions. Comparing the present data with that previously reported, it was found that bezafibrate caused decreased LDL cholesterol in types IIA and IIB but increased levels in type IV. This change was correlated with the initial plasma triglycerides (r = 0.74, P less than 0.0001) and initial plasma LDL cholesterol (r = 0.66, P less than 0.001). It is concluded that varied response of LDL to therapy reflects a complex interaction of metabolic events, including changing rates of VLDL conversion to LDL, lipoprotein compositional changes and effects of therapy on LDL degradation rates.

Adult↗
PubMed1979

The role of lysophosphatidylcholine and apolipoprotein A in the cholesterol-removing capacity of lipoprotein-deficient serum in tissue culture.

Lipoprotein-deficient serum (d greater than 1.21 or 1.25 g/ml fraction) is commonly used to deplete cellular cholesterol from cultured cells and presently we have studied some of the potential promoters of this process. Although serum albumin is the main protein component of the fraction, its cholesterol-removing capacity was quite limited, even in the presence of lysophosphatidylcholine, which is the major phospholipid of the d greater than 1.25 g/ml infranatant of serum. On the other hand, apolipoprotein A1 especially when complexed with lysophosphatidylcholine promoted considerable release of cellular cholesterol. The cholesterol-removing capacity of lysophosphatidylcholine alone was related to the fatty acid chain length and was low when the fatty acid chain length was below C-14. The release of cellular cholesterol is not related to shedding of surface glycoproteins and depends on the presence of suitable acceptors in the medium. Such acceptors were presently found in an ultrafiltrate of serum prepared by membrane filtration. It is proposed that in human serum there are low molecular weight protein-phospholipid complexes (less than 100,000), which can cross the capillary endothelial barrier, in preference to lipoproteins, and promote cholesterol removal from peripheral cells.

Adult↗
PubMed1979

A method for studying plasma transport of vitamin D applicable to hypervitaminosis D.

In man, vitamin D is normally transported on a specific binding globulin (DBP) and on lipoproteins. In addition, binding to albumin occurs in the presence of vitamin D excess. Agarose gel electrohoresis was used to study the binding of radioactive vitamin D to plasma proteins in lipoprotein-free plasma (d greater than 1.21 g/ml). This method completely separates DBP from albumin and thus enables the quantification of vitamin D bound to these proteins in various clinical and experimental conditions. The same method can be used to study the transport of other vitamin D metabolites.

Biological Transport↗