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W Patsch

Publications and source records attributed to W Patsch.

At least 91 records · Page 5Linked to original sources
PubMed1990

Role of thyroid hormones in apolipoprotein A-I gene expression in rat liver.

To study the regulation of hepatic apo A-I gene expression, we measured synthesis and abundance of cellular apo A-I mRNA and its nuclear precursors in livers of hypothyroid and hyperthyroid rats. In hypothyroid animals, both synthesis and abundance of apo A-I mRNA was reduced to half of control values. After injection of a receptor-saturating dose of triiodothyronine into euthyroid rats, apo A-I gene transcription increased at 20 min, reached a maximum of 179% of control (P less than 0.01) at 3.5 h, and remained elevated for up to 48 h. The abundance of nuclear and total cellular apo A-I mRNA increased at 1 and 2 h, respectively, and exceeded the levels expected from enhanced transcription more than two fold at 24 h after hormone injection. Upon chronic administration of thyroid hormones, levels of nuclear and cytoplasmic apo A-I mRNA remained elevated but transcription of the apo A-I gene fell to 42% of control (P less than 0.01). Thus, thyroid hormones rapidly stimulate apo A-I gene transcription. Posttranscriptional events leading to increased stability of nuclear apo A-I RNA precursors become the principal mechanism for enhanced gene expression in chronic hyperthyroidism and may cause feedback inhibition of apo A-I gene transcription. Our results furthermore imply that the majority of hepatic nuclear apo A-I RNA precursors are degraded in euthyroid animals.

Albumins↗
PubMed1990

Variation in concentration of lipids, lipoprotein lipids, and apolipoproteins A-I and B in plasma from healthy women.

The components of total variation--biological, inter- and intra-individual, and analytical--of plasma lipids, lipoprotein lipids, and apolipoproteins A-I and B have been determined in a population of 44 healthy women, ages 18-35 years. Blood was sampled three separate times at three-month intervals, with no restrictions on diet or physical activity during these periods. The greatest inter-individual variances were observed for high-density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, and total plasma cholesterol. Triglycerides had the highest intra-individual variance (CV 22%). The percentage of inter- and intra-individual variances of apolipoprotein A-I concentrations were more reflective of total HDL- and HDL2-cholesterol content than of HDL3-cholesterol. Concentrations of calculated low-density-lipoprotein cholesterol showed a greater inter-individual variation (18.6%) than did apolipoprotein B (10.7%). The laboratory CVs for these analytes were similar to other reported values. From these data, we computed the expected variation for subjects in our study for single and repeated measurements. Such considerations can influence decision-making in the clinical setting or in designing epidemiological studies.

Adolescent↗
PubMed1990

Polymorphic forms of human apolipoprotein[a]: inheritance and relationship of their molecular weights to plasma levels of lipoprotein[a].

The plasma concentration of human lipoprotein[a], Lp[a], is highly correlated with coronary artery disease. The protein moiety of Lp[a], apoLp[a], consists of two apoproteins, apo[a] and apoB-100, linked by one or more disulfide bonds(s). Apo[a], the protein unique to Lp[a], exists in polymorphic forms that exhibit different apparent molecular weights (Mr). Polyacrylamide gel electrophoresis in sodium dodecyl sulfate followed by immunoblotting was used to separate and visualize these different forms and to determine the polymorphic pattern of apo[a] in the plasma samples of 692 individuals. A total of 11 different polymorph bands ranging in Mr from 419 kD to 838 kD could be resolved, but only 1 or 2 bands were present per individual. The polymorphic band pattern for an individual was assigned to 1 of the 66 different phenotype designations representing the total number of possible single- and double-band combinations of the 11 detectable bands. All 11 of the possible single-band phenotypes but only 32 of the 55 possible double-band phenotypes were represented. There were 412 plasma samples (59.5%) that contained a single band, 274 (39.6%) contained two bands, and only 6 (0.9%) had no detectable apo[a] band. A highly significant inverse correlation was found between the Mr of the band(s) present and the plasma apoLp[a] concentration (r = -0.461; rho = 0.0001). The correlation was better between apoLp[a] and single-band (r = -0.495; rho = 0.0001) than double-band (r = -0.382; rho = 0.0001) phenotypes. Of the 274 individuals exhibiting double-band phenotypes, the lower Mr band was more intense in 141 (51.4%), the two bands were equally intense in 85 (31.0%), while the higher Mr band was more intense in 48 (17.5%). Based upon the hypothesis that apo[a] polymorphism is controlled by different alleles at a single locus, the frequency of the 11 alleles determined from the observe phenotypes (low Mr----high Mr) was: band 1) 419 kD, 0.00875; band 2) 489 kD, 0.00510; band 3) 536 kD, 0.0555; band 4) 553 kD, 0.0758; band 5) 613 kD, 0.135; band 6) 680 kD, 0.0824; band 7) 705 kD, 0.104; band 8) 742 kD, 0.151; band 9) 760 kD, 0.246; band 10) 796 kD, 0.128; band 11) 838 kD, 0.00802. The observed distribution of phenotypes in the population was compared by chi-square analysis to that predicted on the basis of simple Mendelian inheritance, and the hypothesis was rejected (chi 2 = 921.7; rho less than 0.001). Significantly, the singleband phenotypes are over-represented in the population compared to that predicted.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoproteins A↗
PubMed1990

Effect of blood collection and processing on radioimmunoassay results for apolipoprotein B in plasma.

We studied the effects of different blood collection and processing procedures on quantification of apolipoprotein (apo) B by radioimmunoassay. High-density lipoprotein subfractions HDL3 and HDL2 and isolated apoA-I did not cross-react in the assay. Analytical recovery of apoB at different doses of very-low- and low-density lipoproteins were complete. Inter- and intra-assay coefficients of variation (CVs) averaged 7.4% and 6.0%, respectively. Blood from 20 subjects was collected into tubes containing EDTA alone or EDTA with antiproteolytic and antioxidant agents; one half of each plasma was separated immediately, half after 3 h at 4 degrees C. Regardless of the addition of protective agents or the time difference in separating plasma from other blood elements, freezing plasma at -70 degrees C decreased apoB content a similar amount, an average of 6.8%. This loss of apoB immunoreactivity was not related to apoB content in fresh plasma. Analysis of variance showed no differential effect on apoB content by the various additions to whole blood or plasma. No additional apoB content was lost in once-frozen aliquots of three human plasma pools during storage at -70 degrees C for up to 18 months. We conclude that concentrations of apoB in human plasma can be measured reliably after long-term storage, although the absolute value may decrease slightly as a result of freezing.

Analysis of Variance↗
PubMed1990

Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy.

To assess whether subclinical hypothyroidism is associated with changes in lipoprotein fractions, 13 patients maintained in a stable state of subclinical hypothyroidism for at least 3 months were studied prior to and 2 and 4 months following restoration of a euthyroid state with incremental levothyroxine sodium therapy. Thyrotropin levels ( +/- SEM) had decreased from 16.6 +/- 3.2 mU/L to 3.1 +/- 0.7 mU/L and 3.2 +/- 0.7 mU/L at 2 months and 4 months. At 2 months, levothyroxine treatment led to a decrease in levels of total cholesterol from 5.5 +/- 0.3 mmol/L (213 +/- 12 mg/dL) to 4.8 +/- 0.3 mmol/L (186 +/- 12 mg/dL), in low-density lipoprotein cholesterol (LDL-C) from 3.7 +/- 0.3 mmol/L (143 +/- 12 mg/dL) to 2.9 +/- 0.3 mmol/L (112 +/- 12 mg/dL), and in apolipoprotein B from 91 +/- 8 mg/dL to 74 +/- 7 mg/dL. At 4 months, levels of LDL-C and apolipoprotein B remained significantly lower than pretreatment values (2.9 +/- 0.2 mmol/L [112 +/- 8 mg/dL] and 75 +/- 6 mg/dL, respectively). While high-density lipoprotein cholesterol (HDL-C), HDL3-C, and apolipoprotein A-I were not significantly affected by levothyroxine therapy, there was a slight trend of increase in HDL2-C during levothyroxine substitution. There was also a tendency for a decrease in triglyceride levels from 1.3 +/- 0.2 mmol/L (115 +/- 18 mg/dL) to 0.9 +/- 0.1 mmol/L (80 +/- 9 mg/dL) at 4 months of levothyroxine therapy. Levels of HDL-C tended to decrease from 4.8 +/- 0.4 mmol/L (186 +/- 15 mg/dL) to 4.5 +/- 0.5 mmol/L (174 +/- 19 mg/dL) at 2 months and to 3.9 +/- 0.4 mmol/L (151 +/- 15 mg/dL) at 4 months. The LDL-C/HDL-C ratio also decreased from 3.3 +/- 0.3 mmol/L (128 +/- 12 mg/dL) to 2.9 +/- 0.5 mmol/L (112 +/- 19 mg/dL) and 2.5 +/- 0.3 mmol/L (97 +/- 12 mg/dL) at 2 months and 4 months, respectively. These results suggest that long-term levothyroxine therapy in patients with subclinical hypothyroidism is associated with a decrease in LDL-C and apolipoprotein B levels that are reflected in a trend of decreases in cholesterol/HDL-C and LDL-C/HDL-C ratios known to have a relationship with coronary artery disease.

Adult↗
PubMed1989

Effect of sucrose diet on apolipoprotein biosynthesis in rat liver. Increase in apolipoprotein E gene transcription.

A sucrose-rich diet stimulates the biosynthesis of very low density lipoproteins in rat liver. This diet also increases the triglyceride content of hepatic very low density lipoproteins and changes their apolipoprotein composition. To study the changes of hepatic apolipoprotein biogenesis in response to such a diet, we measured secretory rates of apolipoproteins A-I, B, and E in cultured rat hepatocytes. In cultures from rats fed the sucrose-rich diet the production of apolipoprotein E was increased 2-fold as compared to controls, whereas the production of apolipoproteins A-I and B was unchanged. The enhanced production of apolipoprotein E could be accounted for by a 2-fold increase in hepatic apolipoprotein E mRNA, as measured by slot blot hybridization. To characterize the mechanisms leading to the increase of liver apolipoprotein E mRNA levels we measured the transcriptional activity of the apolipoprotein E gene in a cell-free transcription system using isolated liver cell nuclei. Transcriptional activity of the apolipoprotein E gene was 7% that of albumin gene transcription in control animals. In rats fed a sucrose-rich diet the transcription rate of the apolipoprotein E gene increased to 140 +/- 11% of controls. There was no change in albumin gene transcription. Thus, a sucrose-rich diet enhances apolipoprotein E biosynthesis in rat liver, at least in part, by stimulating transcription of the apolipoprotein E gene.

Animals↗
PubMed1989

The effect of triphasic oral contraceptives on plasma lipids and lipoproteins.

To determine the effect of triphasic oral contraceptives on plasma lipid transport, 150 nonsmoking women with normolipidemia, ages 18 to 35 years, were randomly assigned to receive one of three contraceptive formulations: (1) ethinyl estradiol, 30, 40, and 30 micrograms/day, each for 6, 5, and 10 days per menstrual cycle, and levonorgestrel, 50, 75, and 125 micrograms/day, each for 6, 5, and 10 days; (2) ethinyl estradiol, 35 micrograms/day for 21 days, and phased norethindrone, 500, 750, and 1000 micrograms/day each for 7 consecutive days; and (3) ethinyl estradiol, 35 micrograms/day for 21 consecutive days, and norethindrone, 500, 1000, and 500 micrograms/day for 7, 9, and 5 days, respectively. A control group consisting of 49 women taking a nonhormonal form of contraception was also included. After 6 months of oral contraceptive treatment, significant increases in plasma triglyceride (28% to 52%) and plasma apolipoprotein B levels (20% to 23%) were observed in each treatment group. The changes in total plasma cholesterol (3% to 10%) and low-density lipoprotein cholesterol values (0% to 11%) were less striking. Changes in total high-density lipoprotein cholesterol levels were statistically insignificant (-2% to -4%); however, high-density lipoprotein2 cholesterol levels decreased by 29% to 33% and high-density lipoprotein3 cholesterol levels increased by 20% to 23%. Concomitantly, plasma apoliporprotein A-1 values increased by 5% to 12%. No consistent significant differences among analyses were observed between and of the groups receiving different oral contraceptives for 6 months.

Adolescent↗
PubMed1989

The hyperlipoproteinemias.

The association of disturbances of plasma lipid transport and atherogenesis has been recognized, and scientific data continue to accumulate to explain this association from a mechanistic viewpoint. A number of recent clinical trials have shown that cholesterol-lowering therapy can prevent the complications of atherosclerosis. Consequently, the attention of physicians to therapeutic intervention has increased and public awareness to plasma cholesterol levels has been heightened. This article summarizes current knowledge of how plasma lipid transport is regulated. The classical primary hyperlipoproteinemias are considered and hyperlipoproteinemias occurring secondary to other diseases are discussed. Standard methods to diagnose the defined genetic hyperlipidemias are outlined, and new approaches to assess risk of atherosclerosis are examined. Finally, the role of dietary measures and drugs in lowering blood lipids and reducing risk of coronary heart disease is delineated.

Apoproteins↗
PubMed1989

A dual-precipitation method evaluated for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 in human plasma.

The dual-precipitation method for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 (Warnick et al., Clin Chem 1982;28:1574) was compared with quantification of cholesterol in HDL2 and HDL3 by zonal ultracentrifugation (Patsch et al., J Lipid Res 1974;15:356-66). For 39 plasma specimens differing widely in their HDL subfraction cholesterol concentration, the coefficient of correlation between the two methods was 0.94 for HDL2-cholesterol, 0.82 for HDL3-cholesterol. Storage of plasma specimens at -70 degrees C decreased the apparent content of HDL3-cholesterol by 5%; no significant changes in HDL2-cholesterol were observed. In frozen plasma, interference by apoB-containing lipoproteins and by lipoprotein(a) was negligible. Mean weight ratios of apoA-I to cholesterol were twice as high for HDL3 as for HDL2, reflecting the increased cholesterol content of HDL2. The study suggests that quantification of HDL2 and HDL3 cholesterol by precipitation is appropriate for use in epidemiological studies.

Apolipoproteins A↗
PubMed1988

Regulation of lipoprotein receptors on a rat hepatoma cell line.

The rat H-35 cultured hepatoma cell line expresses receptors for homologous lipoproteins. In previously reported experiments distinct receptors were identified for chylomicron remnants, HDL and LDL, by direct binding studies that yielded distinctive binding constants, cross competition assays, and by differential inhibitory effects of EDTA and suramin. In the present experiments, the regulation of expression of these receptors was assessed by growing cells either in the presence or absence of lipoproteins in the media and by growing cells to different densities (50-800 micrograms cell protein/dish). LDL binding to cells was increased by lipoprotein deprivation at all cell densities. LDL binding was inversely related to cell density when cells were grown in lipoprotein deficient serum (LPDS) but cell density did not affect LDL binding by cells grown in newborn calf serum (NBCS). By contrast HDL binding was not appreciably different whether cells were grown in NBCS or in LPDS. However, HDL binding was inversely related to cell density by cells grown either in LPDS or in NBCS. Binding of chylomicron remnants was increased by growth in LPDS at all densities, but altering growth density in either culture medium had little effect on the cellular binding of chylomicron remnants. The distinctive effects of these experimental perturbations on the binding of the 3 lipoprotein classes tend to confirm the presence of 3 separate receptor activities. The experiments also demonstrate that the responses at least of some of the receptors of the hepatoma cells in culture resemble those of hepatocytes in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of blood collection and processing on radioimmunoassay results for apolipoprotein A-I in plasma.

We studied the effects of different procedures of blood collection and processing on quantification of apolipoprotein A-I (apoA-I) by radioimmunoassay. ApoA-II and apolipoproteins of low- and very-low-density lipoproteins did not cross react in the assay. Analytical recovery of apoA-I at different doses was complete. ApoA-I concentration in pooled human plasma was stable for as long as a year stored at -70 degrees C. Inter- and intra-assay CVs averaged 7% and 5%, respectively. We collected blood from 20 subjects into tubes containing EDTA alone or EDTA with antiproteolytic agents, then separated the plasma either immediately or after 3 h at 4 degrees C. We tested various formulations of antibacterial, antiproteolytic, and anti-oxidant agents added to plasma, measuring apoA-I concentrations either within 24 h of blood collection or after storage of plasma for 6 weeks at -70 degrees C. No significant difference in the concentrations of apoA-I was found in these specimens, regardless of the conditions studied. We conclude that addition of protective agents other than EDTA is not necessary during blood collection or specimen processing for reliable quantification of apoA-I in fresh or frozen human plasma.

Analysis of Variance↗
PubMed1987

The complete amino acid sequence of proapolipoprotein A-I of chicken high density lipoproteins.

The complete amino acid sequence of proapolipoprotein (proapo) A-I of chicken high density lipoproteins was determined by sequencing overlapping peptides produced by trypsin, S. aureus V8 protease, and cyanogen bromide cleavage. There are 240 amino acid residues in mature chicken apoA-I. By direct sequence analysis of a cyanogen bromide peptide, we also determined the sequence of a 6-amino-acid prosegment which is present at approx. 10% the molar amount of the mature peptide in chicken plasma. Sequence comparison among apoA-I from chicken, human, rabbit, dog and rat, and secondary structure analysis indicate that while the degree of sequence homology is only moderate (less than 50% between chicken and man), there is good conservation of apoA-I secondary structure, especially in the N-terminal two-thirds of the protein in these widely separated species.

Amino Acid Sequence↗
PubMed1987

High density lipoprotein2. Relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase.

Lipoprotein lipase (LPL) activity in postheparin plasma of 38 normolipidemic volunteers was related to the magnitude of postprandial lipemia after a fat meal, to triglyceride content of high density lipoprotein2 (HDL2), to hepatic lipase (HL) activity, and to HDL2 levels. LPL activity correlated indirectly with lipemia, triglyceride content of HDL2, HL activity, and levels of HDL2 but not of HDL3. HL activity correlated directly with lipemia and indirectly with HDL2 levels. Triglyceride content of HDL2 correlated directly with lipemia and indirectly with HDL2 levels. In HDL2, abundance of apolipoprotein (apo) A-II and the apoA-I/apoA-II ratio varied widely. The latter correlated positively with LPL activity and HDL2 levels, and, inversely, with HL activity, lipemia, and triglyceride content of HDL2. The study suggests that HDL-cholesterol is not an independent parameter of lipid transport, but is strongly affected by triglyceride metabolism through lipolytic enzymes, as exemplified by postprandial lipemia that affect both composition and plasma levels of HDL2.

Apolipoproteins A↗
PubMed1986

Effects of insulin on lipoprotein secretion in rat hepatocyte cultures. The role of the insulin receptor.

Insulin inhibits the secretion of lipoprotein components such as triglyceride, phospholipid, and apolipoproteins B and E in primary rat hepatocyte cultures. The aim of this study was to determine whether these hormonal effects are related to the interaction of insulin with its receptor on the surface of cultured hepatocytes. Half-maximal inhibition of secretion of apolipoprotein E and triglyceride occurred at 6 ng/ml porcine insulin, equivalent to a 20% receptor occupancy. When compared to porcine insulin, both guinea pig insulin and desoctapeptide insulin were 60 times less inhibitory on triglyceride and apolipoprotein secretion. These analogs were also 60 times less effective in competing with porcine 125I-insulin for receptor binding. Anti-insulin receptor IgG inhibited binding of porcine insulin to cells in a dose-dependent fashion. However, similar to the hormone itself, it reduced the secretion of triglyceride and apolipoproteins E and B. Preincubation of cells with 200 ng/ml porcine insulin for 15 h caused a 2.5-fold reduction of surface receptor number. These cells were less sensitive to the inhibitory effect of porcine insulin on secretion of triglyceride and apolipoproteins B and E. We conclude that the effects of insulin on lipoprotein processing by hepatocytes in culture are receptor-mediated, can be imitated by antibodies, to the insulin receptor, and are subject to control by receptor down-regulation.

Affinity Labels↗
PubMed1986

Effect of alcohol intake and exercise on plasma high-density lipoprotein cholesterol subfractions and apolipoprotein A-I in women.

Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL2 cholesterol concentrations than inactive women (34 +/- 17 vs 19 +/- 12 mg/dl), but HDL3 cholesterol concentration did not differ between the groups (41 +/- 10 vs 39 +/- 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women.

Adult↗
PubMed1985

Altered HDL subclasses in endogenous hypertriglyceridemia are not affected by weight reduction.

Reduction of body weight is commonly used to decrease the plasma lipids of patients with primary endogenous hypertriglyceridemia, but the effects of stabilized weight reduction on lipoprotein compositions and distribution are not well known. Since lipoprotein structures are perhaps as important in normal and abnormal metabolism and atherogenesis as are the levels of lipoproteins, we examined the effects of weight loss on the plasma concentrations, compositions, and ultracentrifugal flotation properties of plasma lipoproteins. Nine patients (eight males, one female) with endogenous hypertriglyceridemia and low high-density lipoprotein (HDL)-cholesterol levels who were approximately 130% of ideal body weight were studied during two dietary periods (basal and low weight). Subjects consumed an isocaloric diet for 5 weeks consisting of approximately 15% protein, approximately 45% carbohydrate, approximately 40% fat, approximately 500 mg/d cholesterol, P/S ratio 0.43 (basal), followed by a hypocaloric diet of the same composition, which was eaten for 16 to 52 weeks, until the desired weight was lost (9.6 +/- 3.6 kg). Then patients continued to eat a diet of the same composition lower in calories but sufficient in quantity to maintain their new lower body weights for the final 5 weeks (low-weight period). The last weeks of the basal and the low-weight periods were spent in a metabolic ward. Thus, high and low body weights were known to be stable for at least 5 weeks. Fasting (12 to 14 hours) plasma total triglycerides decreased in all patients (from 328 +/- 204 mg/dL at basal to 185 +/- 77 mg/dL at low weight, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗