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Biomedical subjects

H Jansen

Publications and source records attributed to H Jansen.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Improvement of cervical mucus viscoelasticity and sperm penetration with sodium bicarbonate douching.

The aim of the study was to evaluate the influence of vaginal douching with sodium bicarbonate (NaHCO3) upon cervical mucus viscoelasticity and sperm penetration in vitro and in vivo. Twenty-five couples with primary infertility for greater than 12 months participated in the study. The selection criteria were: (i) semen quality compatible with conception, (ii) regular ovulatory cycles and (iii) repeated negative post-coital test (PCT). After at least one inventory cycle, three consecutive cycles were studied. In the second and third cycles, vaginal douching was performed with either 1.5% (w/v) NaHCO3 or 0.9% (w/v) NaCl (randomized procedure). The viscoelasticity of the cervical mucus, sperm penetration tests (SPT) and PCTs were analysed. The viscoelasticity of mucus samples after NaHCO3 douching was significantly lower than the viscosity after NaCl douching (P less than 0.001, n = 16) and in the control cycles (P = 0.003). The SPT scores were significantly higher in the NaHCO3 cycles than in the NaCl cycles (P = 0.004, n = 22) and in the control cycles (P less than 0.001). The PCT scores proved to be significantly higher after NaHCO3 douching than after NaCl douching (P = 0.002, n = 21). Comparison of NaHCO3 and control cycles also showed a significant improvement of the PCT score after NaHCO3 douching (P less than 0.001).

Bicarbonates↗
PubMed1990

Continuous exposure of Suffolk ewes to an equatorial photoperiod disrupts expression of the annual breeding season.

The objective was to determine if "clamping" ewes onto a 12L:12D photoperiod resulted in expression of circannual rhythms of reproductive activity. On 24 February, 1986, two groups of 6 yearling ewes each were placed in isolated adjacent photochambers under a 12L:12D photoperiod and controlled temperature. Six control ewes were kept outdoors. Blood samples taken thrice weekly were analyzed for progesterone. Data from Days 0-1056 are reported. The mean number of cycles by control and 12L:12D ewes did not differ (32.8 +/- 1.7 vs. 29.7 +/- 4.0). The ranges were 27-39 vs. 4-51, respectively. Ten 12L:12D ewes started cycling coincidentally or later than the controls, and then cycled either regularly or irregularly throughout the study. Two of the 12L:12D ewes cycled continuously. The mean number of cycles during the period 15 April-15 August (anestrus) in Years 1, 2, and 3 were 0.7, 0.7, 0.2 for controls versus 0.3, 5.1, and 4.5 for 12L:12D ewes. The mean number of cycles during the period 15 September-15 January (breeding season) in Years 1, 2, and 3 were 7.3, 7.7, and 7.3 for controls versus 2.8, 4.8, and 4.0 for 12L:12D ewes. All controls showed distinct, alternating annual periods of anestrus and ovarian cycles whereas only two 12L:12D ewes showed a similar pattern. Estrous cycles were distributed nonrandomly in all controls and in 2 ewes exposed to 12L:12D. In the 12L:12D ewes, melatonin concentrations rose immediately after the lights-off and fell immediately after on. Lengths of the luteal phases of the cycles did not differ between groups. In summary, estrous cycles of most ewes clamped on a 12L:12D photoperiod occurred throughout the year at variable intervals rather than in distinct breeding seasons.

Anestrus↗
PubMed1990

Results of surgical treatment of severe vesicoureteric reflux. Retrospective study of reflux grades 4 and 5.

A series of 80 children underwent surgery in the Sophia Children's Hospital for gross reflux grades 4 and 5. In this retrospective study the success rate for ureteric reimplantation was 90%. Analysis of growth showed that after surgery the children tended to fall within the normal ranges for height and weight. Deterioration in renal function was progressive in 3 children. New renal scars developed in 13% of renal units. Initially non-refluxing kidneys showed no further deterioration. Moderate hypertension was found in only 4 patients.

Adolescent↗
PubMed1990

Effect of pravastatin on biliary lipid composition and bile acid synthesis in familial hypercholesterolaemia.

Nine patients with heterozygous familial hypercholesterolaemia were treated for eight weeks with either 40 mg pravastatin or placebo under double blind conditions. Six patients received pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Treatment with pravastatin resulted in a significant decrease in plasma cholesterol caused by a decrease in low density lipoprotein cholesterol (LDL-c) of 30% (p less than 0.005). We determined the effect of this medication on the lithogenicity of bile. Cholesterol saturation index of fasting gall bladder bile decreased with 23% (p less than 0.01) from 1.06 to 0.75 during treatment with pravastatin. A reduction of 24% (p less than 0.01) in molar percentage of biliary cholesterol was seen. After treatment the total bile acid excretion in faeces and the molar percentage of biliary bile acids were not significantly changed, suggesting that pravastatin does not influence bile acid biosynthesis to a significant extent. These findings indicate that treatment with pravastatin can decrease the incidence and complications of cholesterol gall stones.

Adult↗
PubMed1990

Analysis of sonographic pattern in prostatic cancer: comparison of longitudinal and transversal transrectal ultrasound with subsequent radical prostatectomy specimens.

In this study the diagnostic accuracy of transrectal ultrasonography (TRUS) in identifying prostatic cancer has been investigated. Attention was paid to the localization of tumor, capsular penetration and involvement of seminal vesicles. TRUS was performed with a 5-mHz linear array longitudinal probe as well as with a 5-mHz rotating transverse scanner. 23 patients underwent radical prostatectomy. The histological results were compared with the sonographic patterns. Transverse TRUS and longitudinal TRUS were comparable with regard to all the investigated parameters. The sensitivity and specificity for the presence or absence of tumor were 70-75 and 54%, respectively. When suspicion of capsular involvement was estimated in a prostatic lobe, a sensitivity of 89% and a specificity of 21% was found. When every separate ultrasonographically suspicious area of capsular breach was considered, there was a positive correlation of 63%. Seminal vesicle infiltration is hard to identify and TRUS has a sensitivity of only 65-74% with a specificity of 40-57%.

Humans↗
PubMed1990

Growth hormone and thyroxine affect lipoprotein metabolism in hypothyroid and hypophysectomized rats.

The aim of this study was to evaluate the effect of thyroxine (T4) and GH replacement therapy on serum lipoproteins in rats with primary and secondary hypothyroidism and to see whether recovery of GH activity was associated with normalization of serum lipoproteins. In both the primary and secondary hypoproteins. In both the primary and secondary hypothyroid rats, total cholesterol (TC) was higher than in normal controls, due to an increase in low-density lipoprotein cholesterol (LDL-c) and to a lesser extent also in high-density lipoprotein cholesterol (HDL-c). Treatment of hypophysectomized rats with GH induced a decrease in the concentration of TC, LDL-c and HDL-c, while liver lipase activity (LLA) increased. The effect of GH on HDL-c was correlated with the increase in LLA. T4 replacement therapy of hypophysectomized rats normalized LDL-c, but HDL-c and LLA were unaffected. During primary hypothyroidism, T4 treatment induced GH activity, increased LLA and reduced the HDL-c concentration. GH treatment of primary hypothyroid rats had a similar influence on the lipid levels and LLA as in hypophysectomized animals, although the lowering of HDL-c was less prominent. These results demonstrate that GH determines serum lipoproteins during both primary and secondary hypothyroidism.

Animals↗