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Biomedical subjects

W Patsch

Publications and source records attributed to W Patsch.

At least 127 records · Page 7Linked to original sources
PubMed1980

Structure, immunology, and cell reactivity of low density lipoprotein from umbilical vein of a newborn type II homozygote.

In this report we compare the cord blood lipoproteins of a newborn boy homozygote who has low density lipoprotein (LDL) receptor-defective familial hypercholesterolemia (FH) with the lipoproteins from cord blood of normal newborns. Plasma LDL-cholesterol and apoprotein (Apo)B were 612 and 233 mg/dl (vs. 31+/-16 and 24+/-12 mg/dl, respectively, for normals, n = 21). LDL-cholesterol/ApoB ratio was 2.6 vs. 1.4+/-0.5. Levels of ApoA-I, ApoA-II, and HDL-cholesterol were similar to normal cord plasma. Thus, the lipoprotein abnormality is apparent at birth and is definitely present in LDL. Abnormalities in other lipoprotein, lipid, and in plasma apoprotein levels were not detected. On zonal ultracentrifugation, FH LDL was comprised of two populations (LDL(a) and LDL(b)), both faster floating than normal cord LDL (LDL(c)). This difference was due to the larger diameters of the particles on electron microscopy (LDL(a) = 276A+/-32 and LDL(b) = 260A+/-38 vs. LDL(c) = 237A+/-26, n = 200 each, mean+/-1 SD), and their higher contents of lipids relative to protein (86 and 82% vs. 74%, LDL(a), LDL(b), and LDL(c), respectively). More than 94% of the protein in both the FH and the normal preparations consisted of ApoB. FH LDL were more effective than control LDL in competing with (125)I-LDL (adult) for limiting amounts of anti-LDL antibodies in radioimmunoassay. FH LDL also competed more effectively for binding to LDL receptors on cultured fibroblasts at 4 degrees C, and FH LDL also delivered more cholesterol into the cells. Cells grown in lipoprotein-deficient serum contained 44+/-2 mug cholesterol/mg cell protein, incubation of cells for 18 h at 37 degrees C in 5 mug/ml FH LDL (protein) or in normal LDL raised cellular cholesterol levels to 75+/-2 and 60+/-2 mug/mg, respectively.LDL isolated from the FH patient's plasma at 6 mo of age and from his brother's plasma (a 5-yr-old boy FH homozygote) were similar to LDL isolated from normolipemic subjects in flotation properties, chemical composition, and immunochemical and cell reactivity. The fact that differences between normal cord LDL and FH cord LDL were present at birth, but that the differences between control and FH LDL were no longer present postnatally suggests that the altered immunologic and cell interactive properties of FH cord LDL were probably related to its unusually high contents of core lipids.

Child↗
PubMed1979

Lipolysis produces changes in the immunoreactivity and cell reactivity of very low density lipoproteins.

Smaller very low density lipoprotein (VLDL) remnants interact more readily with tissues than do larger "intact" VLDL. This may be related to changes in the availability of VLDL apoproteins on the surface of the lipoproteins. To test this hypothesis VLDL were incubated at 37 degrees C with bovine milk lipase (LPL), and the abilities of LPL-treated VLDL preparations to compete with (125)I-low density lipoproteins (LDL) for interaction with cultured normal human fibroblasts were measured. At the same time, the immunologic activities of these preparations were also tested by double antibody radioimmunoassay. Triglyceride (TG) contents of VLDL fell by 30-90% during incubation with LPL and, on zonal ultracentrifugation, VLDL of faster Svedberg unit of flotation (S(f1.063)) rates (>150) were gradually converted to smaller VLDL with lower S(f) rates (21-60). LPL-treated VLDL competed two to five times more effectively with (125)I-LDL for binding to cellular receptors than did control VLDL. Control VLDL incubated with heat-inactivated LPL at 37 degrees C, or with active LPL at 4 degrees C had unaltered cell reactivities and TG contents compared with VLDL incubated without any enzyme. The direct uptake and degradation of LPL-treated VLDL was also assessed by using VLDL (125)I-labeled in apoprotein (Apo)B. LPL-treated VLDL-(125)I-ApoB were taken up and degraded by fibroblast at greater rates than were control VLDL-(125)I-ApoB. Thus, hydrolysis of VLDL lipids was accompanied by an increased ability of VLDL to interact with fibroblasts. The immunoreactivity of ApoB in the same VLDL preparations, expressed as the "apparent ApoB contents" of LPL-treated VLDL, increased by 10-50% (P < 0.02) in those assays that contained anti-LDL antisera, but the ApoB of control VLDL remained constant. However, assays that contained antisera directed against ApoB isolated from VLDL did not distinguish between LPL-treated and control VLDL. Thus, VLDL lipid hydrolysis was accompanied by changes in the immunoreactivity of VLDL-ApoB, which probably reflect changes in the disposition of ApoB on the surface of VLDL. The altered disposition of ApoB on VLDL "remnants" may be related to their enhanced interaction with cells.

Adult↗
PubMed1978

Activation of adipose tissue lipoprotein lipase by lipoprotein fractions from normals and patients with type v hyperlipoproteinemia.

The effects of the main lipoprotein density classes on the human adipose tissue lipoprotein lipase activity were studied. A dose-dependent stimulation of lipoprotein lipase activity was obtained for HDL and, to a lesser extent, for VLDL on a constant weight basis. LDL exerted virtually no effect. At higher concentrations, HDL as well as VLDL inhibited the stimulated lipolytic activity. In type V hyperlipoproteinemia, the stimulating effect of VLDL and of HDL was significantly lower, whereas the inhibiting action of HDL was markedly increased.

Adipose Tissue↗
PubMed1978

Isolation of subfractions of human very low density lipoproteins by zonal ultracentrifugation.

Very low density lipoproteins (VLDL) have been isolated and subfractionated on the basis of their differing flotation rates. The procedure consists of a single 45-min zonal ultracentrifugation step using a linear density gradient of d = 1.00 to 1.15 g/ml. Appropriate fractions of the zonal rotor effluent containing the entire VLDL spectrum were characterized by analytical ultracentrifugation, gel filtration chromatography, and complete chemical analysis. Flotation rates of VLDL subspecies from hypertriglyceridemic and normolipemic plasmas correlated directly with their Stokes radii and triglyceride content and inversely with their proportion of cholesterol, cholesteryl esters, phospholipids, and total protein. There was also an inverse correlation of flotation rate with the fraction of tetramethylurea-insoluble protein. This procedure provides a reliable methodology for a rapid isolation of VLDL subfractions and the accurate determination of their flotation rates.

Centrifugation, Zonal↗
PubMed1978

Initial cholesterol esterification rate in hyperlipoproteinaemia: effects of triglyceride-rich lipoproteins.

The initial cholesterol esterification rate (LCAT activity) was determined in ninety-four hyperlipidaemic subjects. LCAT activity was elevated in hypertriglyceridaemia, whereas patients with hypercholesterolaemia had normal activities. In hypertriglyceridaemic subjects LCAT activity correlated with the concentrations of d less than 1.006 lipoproteins, plasma triglycerides, cholesterol and cholesterol esters and phospholipid levels. Addition of d less than 1.006 lipoprotein to normal plasma resulted in a dose dependent stimulation of enzyme activity with a sigmoidal response curve. When the d less than 1.006 lipoproteins were removed from hypertriglyceridaemic plasma by ultracentrifugation, the enzyme activity in the residual d greater than 1.006 fraction dropped, but still was higher than in normal plasma and correlated with the amount of d less than 1.006 lipoproteins originally present. Thus, high LCAT activity in hypertriglyceridaemia cannot be explained solely by the presence of an increased d less than 1.006 lipoprotein concentration. An increase of enzyme concentration or changes in concentration or composition of other lipoproteins (high density lipoproteins) may contribute to the high LCAT activity in hypertriglyceridaemia.

Adult↗
PubMed1977

Characterization and partial purification of acid lipase from human leucocytes.

Hydrolysis of glycerol trioleate by human leucocytes was characterized and the enzymes responsible for this activity were obtained in a purified form by means of gel chromatography on Sephadex G-100 as well as by zonal ultracentrifugation followed by gel chromatography. The activity is localized in the granule fraction of leucocytes (15 000 X g, 20 min) and shows a sharp pH optimum at pH 5.25. As judged from the elution profile obtained by gel chromatography, two proteins are likely to contribute to the hydrolysis of glycerol trioleate. The approximate molecular weights of the two enzymes are 74 100 and 60 300, respectively. The activity is reduced in the presence of NaCl, KCl, CaCl2 as well as of p-hydroxymercuribenzoate. The enzymes are stable at -25 degrees C but loose about 50% of their activity within 48 h at 4 degrees C.

Cytoplasmic Granules↗
PubMed1977

[The effect of pindolol on carbohydrate and fat metabolism in diabetes mellitus].

Twenty-seven diabetic patients, nine treated with insulin, nine treated with tolbutamid, and nine placed on diet, were given either pindolol or placebo 5 mg, three times daily during a 6-week period. The following 6-week period those receiving pindolol in the first 6 weeks received placebo and vice versa. Pindolol had no influence on the concentration of blood glucose, free fatty acids, triglycerides, or total cholesterol. The effect of pindolol on carbohydrate and fat metabolism appears to be of no clinical relevance in diabetic patients receiving their usual therapy.

Adult↗
PubMed1976

Isolation and partial characterization of two abnormal human plasma lipoproteins: LP-X1 and LP-X2.

Two abnormal lipoproteins (LP-X1 and LP-X2) rich in free cholesterol and phospholipid have been isolated from the plasma of nine different patients with obstructive jaundice. As isolated, both lipoproteins were devoid of low density lipoproteins as judged by agar electrophoresis. In addition, they were free of apoB as judged by double immunodiffusion. However, LP-X1 exhibited a higher phospholipid to protein ratio and a lower hydrated density than LP-X2. The levels of LP-X1 and LP-X2 in plasma were measured in three patients studied for 14 days after corrective surgery for obstructive liver disease. The level of both these abnormal lipoproteins decreased after surgery until the twelfth day when they were completely absent from the plasma of these patients. The rates of this decrease for the two particles are significantly different. These differences in metabolic, chemical, and physical properties of LP-X1 and LP-X2, establish their identity as two distinct and unique lipoprotein particles.

Adult↗
PubMed1976

[The effect of Glipizide on the blood glucose and insulin in non-ketotic diabetes mellitus (author's transl)].

9 patients suffering from non-ketotic diabetes were treated for 7 days with glipizide, a sulphonylurea derivative. A decrease in blood glucose level was observed in 6 patients during the course of the day, accompanied by an increase in immunoreactive insulin during the first half of the day and an increase in the insulinogenic index. In one patient with insulinopenic diabetes glipizide had only a very small effect on the blood glucose and insulin concentration. 2 patients suffering from insulin resistance caused by type IV hyperlipoproteinanemia and obesity showed an increase in insulin, but no decrease in blood glucose concentration. These results are a further indication that sulphonylurea agents should be administered only in the case of certain specific types of diabetes, because no therapeutic response can be expected in diabetes caused by insulinopenia and insulin resistance.

Adult↗
PubMed1976

An enzymatic method for the determination of the initial rate of cholesterol esterification in human plasma.

A method is described for the determination of the initial rate of cholesterol esterification in human plasma, based on the enzymatic determination of free cholesterol in the plasma before and after incubation at 37 degrees C. The cholesterol esterification rate was linear up to 40 minutes. In 18 normal male and 10 normal female subjects the cholesterol esterification rate was 91 +/- 15 (mean +/- SD) and 62 +/- 12 nmoles/hr/ml of plasma, respectively.

Acyltransferases↗
PubMedDate not supplied

Lipoproteins in familial hyperalphalipoproteinemia.

Familial hyperalphalipoproteinemia is determined by a major gene and is characterized by high levels of high density lipoprotein cholesterol and longevity. To describe the plasma lipoproteins in this condition more completely, a kindred consisting of the proband, her affected father, add her two affected brothers was studied. Fasting plasmas were analyzed for lipoprotein lipids by combined preparative ultracentrifugal and precipitation methods. Levels of apolipoprotein A-1 and apolipoprotein A-11, the major apoproteins of high density lipoproteins, were assayed by radioimmunoassay. The flotation properties of very low density, low density and high density lipoprotein were determined by zonal ultracentrifugation, and the isolated high density lipoprotein subfractions were characterized according to their lipid and apoprotein compositions. Total cholesterol of all subjects was normal, but triglycerides were elevated (above the 90th percentile) in the two brothers. High density lipoprotein cholesterol ranged from 150 to 165 mg/dl in the proband and from 72 to 89 mg/dl in her relatives. Apolipoprotein A-1 was 318 mg/dl in the proband and 156 to 169 mg/dl in the siblings; respective apolipoprotein A-11 values were 67 and 82 to 83 mg/dl. The high density lipoprotein cholesterol and apolipoprotein A-1 and A-11 values for the relatives are above the 95th percentile for sex and age, while the levels of the proband are the highest recorded in our laboratories. On zonal ultracentrifugation, very low density lipoprotein and low density lipoprotein had normal flotation properties. High density lipoprotein was divisible into three populations, HDL2, HDL3L, and HDL3D (Sf(1,21,26 degrees C), 59, 2.9, and 1.7 respectively), each of which floated in its usual position. But HDL2 was grossly elevated, accounting for most of the rise in the high density lipoprotein fraction. The compositions of the high density lipoprotein fractions with respect to the major lipid and apoprotein classes did not differ from normal. Thus, in this kindred, high density lipoprotein was quantitatively rather than qualitatively unusual. It is of interest that hypertriglyceridemia and hyperalphalipoproteinemia coexisted in the siblings. These concurrent elevations differ from the expected reciprocal relationship between high density lipoprotein and very low density lipoprotein levels in plasma, and suggests that in some subject the two abnormalities may be independently transmitted.

Apolipoproteins↗
PubMedDate not supplied

Relationship of plasma lipoprotein Lp(a) levels to race and to apolipoprotein B.

Lipoprotein Lp(a) is an atherogenic subfraction of plasma lipoproteins which has been studied predominantly in white populations. We quantified Lp(a) by electroimmunoassay in plasma from 105 black and 134 white healthy men and women. Results were correlated with clinical variables and plasma levels of lipids, other lipoproteins, and apolipoprotein (apo) B determined by radioimmunoassay. Black subjects had levels of Lp(a) that averaged twice those of whites (p less than 0.001). Among blacks, Lp(a) levels showed a bell-shaped frequency distribution, while among whites the distribution was strongly skewed, with the highest frequencies at low levels. Contrary to previously published results, the apo B levels in our study correlated significantly, though weakly, with Lp(a) (r = 0.21, p = 0.001 among whites, and r = 0.15, p = 0.02 among blacks, Kendall rank correlation). The regression slopes and variances suggested that apo B in the Lp(a) lipoprotein could account for the correlation. Lp(a) levels did not correlate significantly with any other plasma lipoprotein or lipid levels. The implications of this study are as follows: Despite the high levels of Lp(a) among blacks in the Houston area, these blacks do not experience greatly increased atherosclerotic progression and mortality. Thus, the atherogenicity of Lp(a) in blacks must be decreased or counterbalanced by other factors. The correlation between Lp(a) and apo B should be taken into account when analyzing atherogenic risk, but this correlation is not strong enough to dispute the independence of Lp(a) and apo B as risk factors.

Adolescent↗