PubMed Health⌕ Search

Biomedical subjects

H Jansen

Publications and source records attributed to H Jansen.

At least 19 recordsLinked to original sources
PubMed1995

Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS).

BACKGROUND: Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients. However, few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment. The Regression Growth Evaluation Statin Study (REGRESS) addresses this group of patients. METHODS AND RESULTS: REGRESS is a double-blind, placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L (155 and 310 mg/dL) by quantitative coronary arteriography. Primary end points were (1) change in average mean segment diameter per patient and (2) change in average minimum obstruction diameter per patient. Clinical events were also analyzed. Of the 885 patients, 778 (88%) had an evaluable final angiogram. Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group (P = .019): The mean difference between treatment groups was 0.04 mm, with a 95% CI of 0.01 to 0.07 mm. The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group (P = .001): The difference of the medians between the treatment groups was 0.06 mm, with a CI of 0.02 to 0.08 mm. At the end of the follow-up period, 89% (CI, 86% to 92%) of the pravastatin patients and 81% (CI, 77% to 85%) of the placebo patients were without new cardiovascular events (P = .002). CONCLUSIONS: In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.

Angioplasty, Balloon, Coronary↗
PubMed1995

Autoantibodies against malondialdehyde-modified LDL are elevated in subjects with an LDL subclass pattern B.

Small low density lipoproteins (LDL) are more susceptible to in vitro oxidation than larger LDL. To study whether this leads to more oxidation of small LDL in vivo, we determined the level of autoantibodies against malondialdehyde-modified LDL (MDA-LDL) in subjects with small or large LDL (LDL subclass pattern B or A) by ELISA. The study group consisted of 92 subjects with coronary heart disease without severe hypercholesterolemia (mean total plasma cholesterol 5.9 +/- 0.8 mM), 46 with an LDL subclass pattern A and 46 with an LDL subclass pattern B. In the subjects with LDL subclass pattern B the titre of autoantibodies of the IgM class against MDA-LDL was 29% higher than in the subjects with LDL subclass pattern A (P < 0.0001). The concentration of the anti-MDA-LDL autoantibodies of the IgM class was 58% higher in the patients with the pattern B than in the patients with the pattern A (P < 0.0001). There was no statistically significant difference in the titre or concentration of autoantibodies of the IgG class between subjects with LDL subclass patterns A and B. Besides plasma triglyceride and HDL cholesterol, the titre and concentration of the IgM autoantibodies were found to be independent predictors of the LDL subclass pattern. These results show that small LDL are associated with higher autoantibody levels than large LDL. Based on the assumption that the level of autoantibodies against MDA-LDL represents the rate of LDL oxidation in vivo, we conclude that in vivo small LDL is more readily oxidised than larger LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1995

A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis.

A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with significantly reduced HDL levels (P = 0.001) and results in a significant decrease in LPL catalytic activity (P < 0.0009). The relative frequency of this mutation increases in those patients with lower HDL cholesterol levels. In vitro mutagenesis and expression studies confirm that this change is associated with a significant reduction in LPL activity. Our data support the relationship between LPL activity and HDL-C levels, and suggest that a specific LPL mutation may be a factor in the development of atherosclerosis.

Adult↗
PubMed1995

High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients.

In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments.

Adult↗
PubMed1994

Hepatic lipase gene is transcribed in rat adrenals into a truncated mRNA.

Rat adrenals contain a lipase activity that is indistinguishable from hepatic lipase (HL) present in liver. Expression of HL mRNA in adrenals was studied using the method of reverse transcription-polymerase chain reaction (RT-PCR). A 596-bp fragment of HL cDNA spanning exons 5 to 8 was amplified when using total RNA from rat adrenals and liver, but not from heart or kidney. The abundance of HL mRNA was quantified by competitive RT-PCR using a standard RNA that was generated in vitro by transcription from a deleted HL cDNA construct. Adrenals contained 0.4 attomoles of HL mRNA per microgram of total RNA, compared to 16 attomoles in liver. In hypertrophic adrenals isolated from corticotrophin-treated rats, the abundance also amounted to 0.4 attomoles of mRNA per microgram of total RNA. However, amplification of full-length cDNA from either control or hypertrophic adrenals was never observed. Detailed analysis by PCR using different combinations of primers indicated that exons 3 to 9 including the 3'-untranslated region were expressed in adrenal RNA, but not the first two coding exons. The upstream part of the adrenal lipase mRNA was cloned after rapid amplification of cDNA ends (RACE). The resulting clones showed a unique 126-bp sequence 5' of the exon 2-exon 3 junction. This sequence contained multiple termination codons in all three reading frames but lacked a potential start codon. RT-PCR using an HL-specific primer and an oligonucleotide directed against this 5'-sequence showed that it is not only expressed in RNA from adrenals but also in liver. Pulse-labeling of freshly isolated adrenocortical cells with [35S]methionine followed by immunoprecipitation with anti-HL antibodies failed to show synthesis of mature HL, but indicated the synthesis of immunoreactive proteins in the 40-45 kDa range that remained mainly intracellular. Hence, the HL gene is transcribed in adrenals but results in an mRNA species with a unique 5'-end. Translation from an internal start site may produce an intracellular HL isoform that differs markedly from the liver-type lipase previously identified in adrenals.

Adrenal Cortex↗
PubMed1992

Opposite regulation of hepatic lipase and lecithin: cholesterol acyltransferase by glucocorticoids in rats.

Rats were treated with hydrocortisone, dexamethasone or triamcinolone for 4 days. The effect of treatment on hepatic lipase and lecithin:cholesterol acyltransferase (LCAT) mRNA levels and catalytic activities was determined. Hepatic lipase mRNA was not affected by hydrocortisone, but was decreased after dexamethasone (-28%) and triamcinolone (-54%). Hepatic lipase activity followed the same pattern, it was not affected by hydrocortisone and lowered by dexamethasone (-38%) and triamcinolone (-70%). The LCAT mRNA level in the liver was also not affected by hydrocortisone, but increased upon treatment with dexamethasone (+22%) and triamcinolone (+72%). Plasma LCAT, determined with an excess exogenous substrate (designated LCAT-II), tended to decrease after hydrocortisone treatment (-11%) and was higher after dexamethasone (+21%) and triamcinolone (+22%). The plasma cholesterol esterification rate (designated LCAT-I), determined by incubation of the plasma at 37 degrees C, followed the same pattern. The activity ratio of hepatic lipase/LCAT-II decreased from 1 in the controls to 0.51 after dexamethasone and 0.25 in the triamcinolone-treated animals. The plasma HDL cholesterol concentration in the different groups changed oppositely to the hepatic lipase/LCAT activity ratio. It is concluded that HDL cholesterol is raised by synthetic glucocorticoids due, among other factors, to a lowered hepatic lipase and an increased plasma LCAT activity. The influence of glucocorticoids on these enzymes is, at least partly, explained by the effects on the hepatic mRNA contents.

Animals↗
PubMed1992

Heparan sulphate proteoglycans are involved in the lipoprotein lipase-mediated enhancement of the cellular binding of very low density and low density lipoproteins.

We found that LPL enhances the binding to HepG2 cells and fibroblasts of both VLDL and apoE free LDL. In the presence of 1.7 micrograms/ml of purified bovine LPL, the binding of LDL and VLDL was up to 60 fold increased as compared to the control binding. In addition, LPL enhances the binding in LDL-receptor negative fibroblasts to the same extent as it does in normal fibroblasts. The presence of 10 mM of EGTA could not prevent the LPL-mediated enhancement of the binding of both LDL and VLDL to fibroblasts, indicating that the binding is calcium independent. Furthermore, up- and down regulation of the LDL receptor did not influence the binding of these lipoproteins in the presence of LPL. Strikingly, we found that the enhancing effect of LPL on the binding of LDL and VLDL to HepG2 cells could be abolished by preincubation of the cells with heparinase, suggesting that heparan sulphate proteoglycans are involved in the LPL-mediated stimulation. We hypothesize that the enhancement of the cellular binding of LDL and VLDL in the presence of LPL is caused by an LPL-bridging between proteoglycans present on the plasma membrane and the lipoproteins, and that the LDL receptor and LRP are not involved.

Cell Membrane↗
PubMed1991

Secretion-coupled increase in the catalytic activity of rat hepatic lipase.

Freshly isolated rat hepatocytes synthesize and secrete hepatic lipase (HL). Comparison of secreted HL with intracellular HL indicates a secretion-linked increase in the specific enzyme activity. (a) Immunotitration with polyclonal anti-HL showed a 3-5-fold lower specific enzyme activity of intracellular HL than of secreted HL. This was confirmed by ELISA using a mixture of monoclonal anti-HL's. (b) After isolation on Sepharose-heparin, a similar difference in specific enzyme activity was observed, whereas the apparent Km for glyceroltrioleate was not different. (c) HL activity secreted in the absence of protein de novo synthesis was 5-fold higher than was accounted for by the fall in intracellular activity, whereas HL protein lost from the cells was near-completely recovered in the extracellular medium. (d) The presence of inactive HL protein was demonstrated in cells treated with castanospermine, which inhibits secretion of newly synthesized HL by interfering with maturation at an early stage of N-linked oligosaccharide processing. Upon removal of castanospermine, secretion of HL activity recovered, even when protein de nove synthesis was inhibited, strongly suggesting that part of the inactive HL was mobilized and became activated. This secretion-coupled increase in HL activity in the absence of protein synthesis suggests the existence of inactive precursor within rat hepatocytes. The catalytic activity of HL becomes apparent upon maturation of the protein after oligosaccharide processing by the rough endoplasmic reticulum glucosidases.

Animals↗
PubMed1991

The effects of probucol on lipoprotein metabolism in the rat.

The effects of probucol on liver and intestinal apolipoprotein, LDL-receptor and hepatic lipase gene expression, as well as plasma lipid and apolipoprotein levels and liver lipase activity were evaluated in male rats. Administration of probucol decreased plasma triacylglycerols, without affecting plasma cholesterol. Plasma apo E and apo B concentrations increased after probucol. Since liver and intestinal apo B and apo E mRNA levels remained unchanged, this increase could be attributed to a delayed clearance by the LDL-receptor, whose mRNA levels dropped by 50% in the liver. For the HDL-apolipoproteins, only liver apo A-IV mRNA levels decreased after probucol, which was reflected by a fall of plasma apo A-IV. Neither hepatic lipase activity nor mRNA levels were significantly influenced by probucol.

Animals↗
PubMed1991

Monitoring human basophil activation via CD63 monoclonal antibody 435.

On activation of human basophilic granulocytes with anti-IgE or with the chemotactic peptide, formyl-methionyl-leucyl-phenylalanine, the expression of the CD63 antigen on the cell surface, detected by monoclonal antibody (MAb) 435, increased up to 100-fold. The kinetics of CD63 up regulation and histamine release were identical, and a strong correlation was found between percentage of MAb 435-binding basophils and extent of histamine release. Immunoelectronmicroscopy demonstrated that the epitope for MAb 435 in resting basophils is located on the basophilic granule membrane. After basophil activation, MAb 435 bound to the exterior of the plasma membrane. Experiments with various doses of anti-IgE demonstrated that the binding of MAb 435 to basophilic granulocytes follows an all-or-nothing-like response per cell. Basophils either do not bind the MAb at all, or they bind a maximal amount of the MAb. We also measured the up regulation of the CD11/CD18 leukocyte adhesion complex. Here, too, we noted an increase in cell-surface exposure of all subunits after activation. This increase was not as strong as increase found with MAb 435. Thus, MAb 435 is an interesting new tool for investigating the activation of human basophils, in addition to the measurement of mediator release. This MAb may be useful for the detection of basophil activation in vivo.

Antibodies, Monoclonal↗
PubMed1991

Effects of the selective alpha 1-antagonist, doxazosin, on hepatic lipid levels and metabolism in the golden hamster.

The effect of the selective alpha 1-antagonist, doxazosin, on lipid metabolism was studied in cholesterol-fed golden hamsters. The hamsters were studied after short-term (1 week) and long-term (6-8 weeks) treatment. Doxazosin was added to the food (0.05-0.1%). Doxazosin lowered, within 1 week, plasma cholesterol and triglyceride concentrations by 12 and 19%, respectively. These effects were slightly larger during long-term treatment (cholesterol by 15% and triglycerides by 27%). Lipoprotein lipase (LPL) activity in postheparin plasma or in adipose tissue or heart was affected by doxazosin. The hepatic triglyceride secretion rate was lowered by 40%. Doxazosin treatment partially prevented the accumulation of cholesterol and triglycerides in the liver. Hepatic cholesterol synthesis was decreased by 25-40%. When determined under optimal conditions, i.e., after prior dephosphorylation, the hepatic microsomal HMG-CoA reductase activity was lowered by 10-25% in the doxazosin-treated animals. However, if HMG-CoA reductase was determined under conditions to prevent phosphorylation and dephosphorylation of the enzyme, representing the in situ expressed activity, the activity in the doxazosin-treated animals was 40% lower than in the controls. These results indicate that the plasma lipid-lowering effect of doxazosin is largely due to its interference with hepatic lipid metabolism and that one of the effects is a lowering of hepatic cholesterol synthesis, probably due to an increase in the phosphorylation grade of HMG-CoA reductase.

Adrenergic alpha-Antagonists↗
PubMed1990

Inhibition of carnitine palmitoyltransferase leads to induction of 3-hydroxymethylglutaryl coenzyme A reductase activity in rat liver.

The relation between carnitine palmitoyltransferase (CPT) activity and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity was investigated. Rats were treated with aminocarnitine or 1-carnitine overnight. In rats, in which CPT activity was inhibited by aminocarnitine, plasma and hepatic triacylglycerol contents were increased 5- to 6-fold. The plasma cholesterol concentration was unchanged, while the hepatic cholesterol content was lowered (-16%). Hepatic cholesterol synthesis, determined by following the incorporation of 14C-acetate and 3H2O into digitonin-precipitable sterols, in liver slices was increased 5- to 7-fold. HMG-CoA reductase activity in liver microsomes was increased to the same extent.

Acyltransferases↗
PubMed1990

Inhibition of hepatic lipase activity impairs chylomicron remnant-removal in rats.

[4-14C]Cholesteryl oleyl ether-labeled chylomicron remnants were injected into rats which received a specific goat antibody against rat hepatic lipase or a control serum. Chylomicron remnant cholesterol ether disappeared from circulation with a significantly higher half-life (2-fold) in antibody-treated rats than in controls (P less than 0.001). Recovered radioactivity in the liver was 2-fold lower in antibody-treated rats (22.8% (n = 6) vs. 45% (n = 4) P less than 0.01). These results clearly show that hepatic lipase may strongly promote chylomicron remnant cholesterol ether uptake by the liver.

Animals↗