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Biomedical subjects

M Fainaru

Publications and source records attributed to M Fainaru.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1986

Effect of moderate isocaloric modification of dietary carbohydrate on high-density lipoprotein composition and apolipoprotein A-1 turnover in humans.

Plasma lipid and apolipoprotein (apo) levels were determined in five normolipidemic subjects and five patients with Type IV hypertriglyceridemia (HTG) who were fed for greater than or equal to 6 weeks on two isocaloric diets. The first diet contained carbohydrates (CHO) as 55% of total calories, 29% as fat and 16% as protein. The second diet contained 40% CHO, 45% fat and 15% protein in normolipidemic subjects and 40% CHO, 41% fat and 19% protein in patients with HTG. All diets had a cholesterol content of approximately 400 mg/day and a polyunsaturated/saturated fatty acid ratio of approximately 1:0. Apo A-1 kinetics were measured during the last 2 weeks of each dietary period. The composition and distribution of high-density lipoproteins (HDL), subclasses HDL2 and HDL3, were determined at the end of each dietary term. In the HTG patients, administration of a 40% compared with 55% CHO diet caused a significant decrease of plasma triglyceride levels and an increase of HDL-cholesterol; low-density lipoprotein (LDL) levels increased and very low-density lipoprotein (VLDL) levels decreased (P less than 0.01 and less than 0.07, respectively). Similar quantitative changes of VLDL and HDL levels were found in the normolipidemic subjects. No significant change in plasma levels of apo A-I, A-II and E occurred. Apo A-I kinetic studies revealed decreased synthetic rates and fractional catabolic rates on the low CHO diet. Separation of HDL subfractions by zonal ultracentrifugation in both groups revealed an increase in HDL3-cholesterol ester and protein, and a decrease in HDL2 protein, phospholipid and cholesterol. Our findings indicate that moderate changes in dietary CHO and fat content affect HDL levels, composition and apo A-I metabolism.

Adult↗
PubMed1985

Aggregation of plasma lipids and lipoproteins in families with and without coronary heart disease.

Familial aggregation of total plasma cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) was analyzed in 37 families with incidence cases of first myocardial infarction (MI), in 154 families of coronary heart disease (CHD) prevalence cases and in control families. Fasting plasma lipid levels were adjusted for age, sex, country of origin and season of year. Mean TC, LDL-C and TG levels were higher among cases, their spouses and among 17-year-old children of incidence cases than among control families. HDL-C was lower among cases and among wives of incidence cases than in their controls. No differences in HDL-C were noted among children. Mid parent-child correlations for TC and LDL-C were higher in 32 families of men who had a MI (r = 0.43 and r = 0.49) than for control families (r = 0.32 and r = 0.29, respectively). When the 5 families of mothers who had a first MI were included in the analysis, the case-child correlations for TC and LDL-C were 0.60 and 0.68, respectively. Father-child correlation for HDL-C was significantly lower (r = -0.17) among the MI incidence case families than among the control families (r = 0.22; P less than 0.05). No substantial differences in familial correlations for lipid variables were noted in the CHD prevalence families and their controls. These findings suggest that total cholesterol and LDL-C levels, but not HDL-C levels, may be a risk marker in adolescents. The associations evident in adolescent children of families with MI incidence cases were not apparent in children whose parents had CHD on entering the study. This could be due to the probably greater misclassification of CHD prevalence cases than MI incidence cases, the awareness in patients with CHD and subsequent behavioural changes, to possible differences in patterns of survival in the two categories, or may reflect a chance finding.

Adolescent↗
PubMed1984

The effects of prednisone therapy on plasma lipoproteins and apolipoproteins: a prospective study.

The effect of prednisone therapy on plasma lipoproteins and apolipoproteins A-I, A-II, and E levels was studied prospectively in a heterogeneous group of six male and six female subjects. All patients were in a good general condition. The patients had normal hepatocellular, renal, and thyroid functions. During the first month of therapy, the following changes were noted: Plasma triglyceride (TG) levels increased slightly in female patients only. In the entire group, plasma cholesterol level increased (17.3% of initial value, P less than 0.01). Plasma high-density lipoprotein cholesterol (HDL-C) level increased by 68% (P less than 0.001), while plasma low-density lipoprotein cholesterol (LDL-C) level increased by only 10.9% (not significant), resulting in an increased ratio of cholesterol in the two (P less than 0.01). No change in levels of plasma apolipoproteins A-I, A-II, and E was evident. The ratio of HDL-C to plasma apolipoprotein A-I increased (P less than 0.01), indicating an increased lipid to protein ratio for this lipoprotein. Most of these changes were already apparent and significant 48 hours after initiation of treatment and persisted throughout the follow-up period (up to 18 months in some patients). Our results show that in patients with no major metabolic abnormality, prednisone induces significant changes of the lipoprotein system, especially in HDL.

Adult↗
PubMed1984

Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.

The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation of bezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3. HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted of free and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL. Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships. The observations support the concept that most abnormalities reflect the degree of triglyceridemia. We suggest that plasma core-lipid transfer protein(s) is an effector of the abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events.

Adult↗
PubMed1983

Distribution of actin, myosin and actin binding protein in platelets of patients with hyperlipoproteinemia.

Significant anomalies in the quantity and relative distribution of the contractile proteins actin, myosin and actin binding protein (ABP) were observed in platelets obtained from patients with hyperbetalipoproteinemia (type IIa) and in patients with hypertriglyceridemia (type IV). Changes were observed in unfractionated platelets, (increased ABP in type IIa patients and increased actin in both type IIa and type IV) in isolated platelet membranes (increased ABP and actin in type IV, and increased myosin in type IIa) and in the KCl extract of platelets (increased actin in type IV and increased myosin in type IIa). The myosin ATPase specific activity was increased in platelets of type IV patients. No changes were observed in the concentrations and distribution of membrane glycoproteins in the platelets of these patients. The above anomalies in the contractile proteins might be relevant to the known functional anomalies of the platelets of patients with hyperlipoproteinemias.

Actins↗
PubMed1982

Structural and metabolic heterogeneity of beta-very low density lipoproteins from cholesterol-fed dogs and from humans with type III hyperlipoproteinemia.

Cholesteryl ester-rich beta-very low density lipoproteins (beta-VLDL) are beta-migrating lipoproteins that accumulate in the d < 1.006 g/ml fraction of plasma from cholesterol-fed animals and from patients with Type III hyperlipoproteinemia. They can be separated from pre-beta-migrating very low density lipoproteins in the d 1.006 g/ml fraction by Geon-Pevikon block electrophoresis. The beta-VLDL have a general property of stimulating cholesteryl ester synthesis and accumulation in macrophages. In the present study, we demonstrated that beta-VLDL obtained from cholesterol-fed dogs fasted for 16 hr were heterogeneous and that two subpopulations of particles, referred to as Fractions I and II, could be isolated from the whole beta-VLDL fraction using gel filtration chromatography. These fractions of beta-VLDL were similar in that both were cholesteryl ester rich, had beta-electrophoretic mobility on Geon-Pevikon electrophoresis, and possessed the B and E apoproteins as major constituents. However, Fractions I and II differed in size, shape, electrophoretic mobility, chemical composition, and apoprotein B type. (Fraction I vs. Fraction II: size: 90 to 300 nm vs. 20 to 70 nm; shape: irregular with redundant surface vs. spherical; electrophoretic mobility on paper: origin vs. beta; chemical composition: rich in phospholipid and poor in protein vs. rich in protein and poor in triglycerides; apoprotein B types: equal amounts of the high and low molecular weight forms vs. predominantly the high molecular weight form.) Furthermore, Fraction I was 3- to 15-fold more active than Fraction II in stimulating cholesteryl ester formation in mouse peritoneal macrophages. The concentration of Fraction I, but not Fraction II, was diminished in plasma by prolonged fasting, and Fraction I transported more intestinal-absorbed retinol than Fraction II. In addition, the plasma clearance of Fraction I injected into cholesterol-fed dogs was distinctly different from the clearance of Fraction II, and the in vivo dieaway of Fraction I resembled that of chylomicrons and chylomicron remnants. These findings suggest that beta-VLDL in dogs are composed of cholesteryl ester-rich chylomicron remnants (Fraction I) and cholesteryl ester-rich lipoproteins, probably of liver origin (Fraction II). Finally, in studies of two patients with Type III hyperlipoproteinemia, we also identified the existence of two fractions in the beta-VLDL with characteristics similar to Fractions I and II of cholesterol-fed dogs.-Fainaru, M., R. W. Mahley, R. L. Hamilton, and T. L. Innerarity. Structural and metabolic heterogeneity of beta-very low density lipoproteins from cholesterol-fed dogs and from humans with Type III hyperlipoproteinemia.

Animals↗
PubMed1982

Correlates of biochemical variables in the Jerusalem Lipid Research Clinic population.

The associations of sex, age and ethnic origin with hematocrit and biochemical variables were studied in the Visit 2 population of the Jerusalem Lipid Research Clinic--1,709 adults and 1,248 17-yr-olds. Differences in globulin, alkaline phosphatase, creatinine and uric acid levels were statistically significant by ethnic origin in both youngsters and adults. Differences by sex and age in many of the variables studied suggested hormonal effects that were more pronounced before the age of menopause. The data presented, relating to a multiethnic free-living population, may provide a useful reference for physicians in this region for distributions of these variables in the population.

Adolescent↗
PubMed1981

Secretion of lipoproteins, apolipoprotein A-I and apolipoprotein E by isolated and perfused liver of rat with experimental nephrotic syndrome.

Nephrotic syndrome induced in the rat by the administration of puromycin aminonucleoside is accompanied by a hyperlipoproteinemia characterized by an elevation of all plasma lipoproteins, particularly of VLDL (1.006 g/ml) and HDL1 (1.050-1.090 g/ml). The increase of HDL1 is due to the accumulation of a lipoprotein species floating mainly in the density interval 1.050-1.090 g/ml, in which apolipoprotein A-I replaces apolipoprotein E as the major constituent peptide. This lipoprotein has been designated nephrotic HDL. The present study was conducted to establish whether nephrotic liver secreted more lipoproteins than the control liver and, in addition, produced a lipoprotein similar to nephrotic HDL found in plasma. Isolated livers from control and nephrotic rats were perfused with a lipoprotein-free medium for 3 h in a recirculating system. Lipoproteins were isolated by ultracentrifugation; apolipoprotein A-I and apolipoprotein E were measured in the whole perfusate at various time intervals. Nephrotic liver secreted twice as much VLDL and HDL2 and 30% more LDL and HDL1 than the control liver. This was accompanied by an increased secretion of both apolipoprotein A-I and apolipoprotein E, the levels of which were 6.5- and 2-fold, respectively, of those found in the control perfusates at the end of the perfusion. In view of the increased secretion of apolipoprotein A-I, the apolipoprotein A-I to apolipoprotein E ratio was much higher in the perfusates of nephrotic livers than in those of the controls. The concentration of apolipoproteins A-I and E in plasma of nephrotic rats was 7- and 2-fold, respectively, of that found in the plasma of the controls. In the perfusates of the nephrotic livers, we could not find a HDL1 (1.050-1.090 g/ml) rich in apolipoprotein A-I similar to that isolated from plasma (nephrotic HDL). We suggest that the latter is formed in the circulation from the intravascular modification of HDL2 secreted in excess by the liver.

Animals↗
PubMed1981

Apolipoproteins in human fetal blood and amniotic fluid in mid-trimester pregnancy.

To examine the potential for prenatal diagnosis of genetic lipoprotein metabolic defects (e.g. abetalipoproteinemia. Tangier disease) we determined the normal concentrations of apolipoproteins (apo) A-I, A-II, B, and E in mid-trimester amniotic fluid and fetal plasma. The concentrations of apo A-I and apo A-II in amniotic fluid were 1--2 per cent of the respective levels in the mother's plasma, whereas apo B and apo E were undetectable in amniotic fluid. In contrast to amniotic fluid, all four apolipoproteins were detectable in fetal plasma, and the levels of apo A-I, apo B and apo E were in the range observed in the mothers: 160.2 +/- 103.1, 59.8 +/- 35.7 and 5.7 +/- 3.5 mg/dl respectively (mean +/- SD, n = 13). The fetal plasma level of apo A-II (28.3 +/- 12.4 mg/dl) was two-thirds that observed in the mother's plasma. The normal levels of these apolipoproteins in fetal plasma are well above the sensitivity of the methods, and their quantification requires only 10--20 microliters of fetal plasma. Determination of apolipoproteins in fetal blood obtained by fetoscopy thus may provide a method for the prenatal diagnosis of congenital apolipoprotein deficiencies.

Adult↗
PubMed1981

Isolation and characterization of lipid-protein complexes present in commercial albumin preparations.

Most commercially available albumin preparations examined by us contain phospholipids, cholesterol and apolipoprotein impurities. As these albumin preparations are frequently used in large amounts in systems involving lipoprotein metabolism these impurities may reach remarkable levels to introduce exogenous effects in these studies. We have studied in detail tow bovine albumin preparations differing in their content of these contaminants. Using preparative ultracentrifugation, we have isolated from both albumins a lipid protein complex at a buoyant density of d = 1.063-1.21 g/ml with a chemical composition resembling plasma high density lipoproteins. This complex when further characterized proved also to have a similar apoprotein composition to bovine plasma high density lipoproteins. Electron microscopic study of this complex revealed discoidal particles closely resembling nascent high density lipoproteins recovered from rat liver or lymph. The similarity of these lipid-protein complexes to high density lipoproteins, accounts for some reported effects caused by commercially available albumin preparations on cholesterol excretion from cells in tissue culture and their ability to act as acceptors for surface remnants released upon VLDL catabolism in vitro.

Apolipoprotein A-I↗