Search PubMed⌕ Search

Biomedical subjects

H Jansen

Publications and source records attributed to H Jansen.

At least 127 records · Page 7Linked to original sources

Circulating and liver-bound salt-resistant hepatic lipases in the golden hamster.

The serum of male golden hamsters was found to contain a circulating triacylglycerol hydrolase activity (serum lipase). In vitro, the enzyme activity was slightly activated by 1 M NaCl (+20%) and inhibited by rat serum (-29%). The hamster liver contained an enzyme with similar characteristics (liver lipase). This enzyme was released into the circulation after intravenous administration of heparin. Both lipase activities were further characterized and compared. The serum lipase had a pH optimum of 9, which was higher than that of the liver enzyme (pH 8.0). The serum enzyme did not bind to Sepharose-heparin columns in contrast to the liver lipase, which could be eluted from the column with 0.75 M NaCl. A polyclonal antibody preparation raised against the heparin-releasable salt-resistant lipase from rat liver inhibited both the hamster serum enzyme and the liver enzyme completely. The affinity of the antibodies towards the hamster enzymes was lower than the affinity towards the rat liver enzyme, but similar with that towards the hamster enzymes in the serum and the liver. A panel of five monoclonal antibodies raised against the rat enzyme did not bind either of the hamster enzymes. If the hamsters were fed a normal lab chow, the lipase activity in the serum amounted up to 110 +/- 20 mU (mean +/- S.D., n = 16) per ml serum (about 600 mU per animal), the liver contained 200 +/- 41 mU per g tissue (total about 800 mU per animal). In animals fed a cholesterol-enriched diet, the serum activity increased by 82% and the liver activity by 27%.

Animals↗

Structural heterogeneity of a human melanoma-associated antigen.

The biosynthesis, structure, and topology of a melanoma-associated antigen, previously defined with the monoclonal antibody NKI/C-3 was studied. A polyclonal rabbit antiserum was raised against the antigen with a broader reactivity than the previously used monoclonal antibody NKI/C-3. The antigen was shown to consist of a single protein backbone to which two or three N-linked glycans were added cotranslationally. Extensive further heterogeneity was generated in the Golgi compartment and was shown to be dependent on the presence of complex type sugars. Although the antigen is associated with melanomas, it was not codistributed with the tyrosinase activity associated with melanogenesis. The antigen did show codistribution with cathepsin D, which is a marker for lysosomal functions.

Antibodies, Monoclonal↗

Increased liver lipase activity in rats with essential fatty acid deficiency.

Liver lipase activity was measured in EFA-deficient rats (long-term) and in control rats and rats fed an EFA-deficient diet for two weeks (short-term). Liver lipase activity was significantly enhanced by EFA deficiency, both in long-term and short-term experiments. The enhanced liver lipase activity could be normalized by feeding these rats normal laboratory chow for 14 days. Since during EFA deficiency prostaglandin synthesis is impaired, the possible involvement of prostaglandins in the observed changes in liver lipase activity during EFA deficiency was studied. Administration of the prostaglandin synthesis inhibitor indomethacin (5 mg/kg body weight, i.p.) to normally fed rats for two days led to an increase of liver lipase activity. Prostaglandin E2 was found to inhibit the secretion of liver lipase activity by freshly isolated parenchymal liver cells in vitro. These results indicate that the increase in liver lipase activity during EFA deficiency may be due to an impairment of the prostaglandin synthesis.

Animals↗

Inhibition of hepatic cholesterol synthesis by the alpha 1-adrenoceptor blocker doxazosin in the hypercholesterolemic golden hamster.

The effect of treatment with the alpha 1-specific adrenoceptor blocker, Doxazosin, on lipid parameters was studied in male Golden hamsters fed a cholesterol-enriched diet. Within 1 week the Doxazosin-treated animals had a lower plasma (-12%) and hepatic (-30%) cholesterol content than the cholesterol-fed controls. De novo cholesterol synthesis in the liver was lowered by 39% in the Doxazosin-treated animals. These data indicate that the reported beneficial effect of alpha 1-blockade on plasma cholesterol levels may be due to lowering of the hepatic cholesterol synthesis.

Acetates↗

Treatment system for whole bladder wall photodynamic therapy with in vivo monitoring and control of light dose rate and dose.

A system is described for in vivo monitoring and control of light dose rate and dose during whole bladder photodynamic therapy (PDT). A modified cystoscope admits an isotropic light source (fiber with diffusing tip, connected to a dye laser) and three translucent nylon catheters that are unfolded in three directions along the bladder wall. An isotropic light detector (0.8 mm. diameter probe on 200 microns. fiber) is inserted into each catheter and connected to an amplifier displaying light dose rate (in mW/cm.2) and integrated light dose (in J/cm.2) for each probe. Before treatment a low light level is used to optimize the position of the light source, requiring equal readings by each of the three dosimetry probes. Uniformity of irradiation is checked by moving the probes through their respective catheters along the bladder wall. With red light (wavelength 630 nm.) a dose rate uniformity of +/- 20% could be achieved in vivo in dog bladder. With green light (514.5 nm.) uniform irradiation was difficult, most likely due to a much smaller contribution of scattered light. Measurements during clinical PDT show that optimizing the light source position by suprapubic transvesical ultrasound may not secure uniform irradiation. Half-way into the treatment a difference of 100% between the readings of two probes was noted. Adjusting the position of the light source resulted in integrated light dose variations of less than 20% among the three probes at the end of treatment.

Animals↗

Effects of doxazosin on lipids, lipoprotein lipases, and cholesterol synthesis in the golden hamster.

The effects of treatment with adrenoceptor blockers on sites regulating lipid metabolism were studied in golden hamsters. In hamsters fed a standard chow, doxazosin, propranolol, and atenolol did not affect plasma cholesterol or triglycerides. After hypercholesterolemia was induced by feeding a cholesterol-enriched diet, doxazosin lowered plasma cholesterol by 12%. Lipoprotein lipase activity in adipose tissue and in the heart was not changed by any of the treatments. Hepatic lipase activity in the liver and blood was lowered by 31% in the doxazosin-treated animals. Hepatic cholesterol synthesis, measured as acetate incorporation into cholesterol and hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity, was also lowered in the doxazosin-treated hamsters. After norepinephrine administration to cholesterol-fed hamsters, atenolol increased (+8%) and doxazosin decreased (-35%) plasma triglycerides. Plasma cholesterol levels and hepatic cholesterol synthesis were no longer significantly affected by doxazosin. In norepinephrine-treated animals, adipose tissue lipoprotein lipase activity was enhanced (+30%) by doxazosin. Hepatic lipase activity in plasma and liver, which was lowered by norepinephrine, was increased by doxazosin. In hamsters not treated with norepinephrine, adrenoceptor blockers had no effect on plasma insulin or thyroid hormone, but with norepinephrine, levels of both insulin and thyroid hormone were increased by doxazosin. These data indicate that selective alpha 1-inhibition with doxazosin may interfere with lipid metabolism at several regulatory sites. The effects depend to a large extent on nutritional and hormonal status. Doxazosin might exert these effects partly via influences on other hormones.

Adrenergic alpha-Antagonists↗

Relationship between insulin-like growth factor-I and low-density lipoprotein cholesterol levels in primary hypothyroidism in women.

The effect of insulin-like growth factor-I (IGF-I) on the disturbance of lipid metabolism during primary hypothyroidism was studied in 12 women with primary hypothyroidism. Significant increases in both low-density lipoprotein (LDL) cholesterol and intermediate-density lipoprotein cholesterol were seen. Lipoprotein concentrations reverted to normal after substitution with thyroxine (T4) until the euthyroid state was reached. A decrease in IGF-I of 65% (P less than 0.005) was seen in hypothyroid patients and this was inversely correlated (r = -0.75; P less than 0.01) with the concentration of LDL cholesterol. Multivariate regression analysis of LDL cholesterol against IGF-I and free T4 showed that IGF-I determines the concentration of LDL cholesterol instead of free T4. Our data suggest that in hypothyroidism, IGF-I is a determinant of the concentration of LDL cholesterol. In addition, hypothyroidism can influence plasma lipoprotein metabolism by lowering the activity of the salt-resistant lipase (liver lipase).

Adolescent↗

A comparative survey of synaptic changes in the rod photoreceptor terminals of rd, rds and double homozygous mutant mice.

In the developing retina of homozygous rd/rd mutant mice the time of onset of degenerative changes and the period of rapid photoreceptor cell loss overlaps the later phase of differentiation during which the maturation of the receptors and the completion of the synaptic connections take place. It remains unresolved if the retarded synaptogenesis within the photoreceptor terminals of the rod cells is a direct effect of the mutant gene or an indirect consequence of premature cell death. In the retina of homozygous rds/rds mutant mice early indication of gene expression within the photoreceptor cells is also recorded as photoreceptor outer segments fail to develop. However, during the very slow rate of degeneration, the surviving cells develop normal synaptic contacts within their terminals. Furthermore, some of the rod cells, though not the cones, go on to enlarge their synaptic structures as more and more photoreceptor cells are lost. In the retina of double homozygous mutant rd/rd;rds/rds mice the photoreceptor cells remain lacking in outer segments, as would be expected, but curiously enough, survive longer than in the rd/rd retina. Among this population of photoreceptor cells with extended life-span profiles of rod terminals are frequently encountered which contain a normal synaptic structure - one synaptic ribbon with two laterally placed processes of horizontal cells and one medially facing process of a bipolar cell. A number of these terminals also show signs of synaptic enlargement. Thus it can be concluded that some of the terminals of the rod photoreceptor cells of the double homozygous rd/rd,rds/rds mice, which survive longer than in the rd/rd mice, develop synapses that are either comparable to normal or resemble those of the rds/rds retina. These findings suggest that retarded synaptogenesis within the rod terminals of the rd/rd retina is likely to result from a pathogenic defect affecting the whole cell and is not due to a specific or exclusive action of the mutant gene on the synaptic components involved.

Animals↗

The effect of very low energy diets on the fatty acid composition of serum lipids.

The fatty acid composition of serum phospholipids, cholesteryl esters and triglycerides was measured in 11 obese individuals before and after 2 and 4 weeks treatment with a liquid diet providing about 600 kcal and 70 g protein per day. The patients received 20g of lipid, which was either maize oil and safflower oil (6 patients) or maize oil and evening primrose oil (5 patients). During treatment serum phospholipid linoleic acid (C18:2n-6) concentration remained constant, the dihomo-gamma-linolenic acid (C20:3n-6) concentration decreased by 44 percent in the safflower oil group and by 37 percent in the evening primrose oil group and the arachidonic acid (C20:4n-6) increased by 26 percent in the safflower oil group and by 20 percent in the evening primrose oil group. The increase in phospholipid arachidonate showed a significant positive correlation with total weight loss during the treatment period. These results suggest that during weight reduction there is a increased mobilization of arachidonic acid from tissues and a decreased rate of linoleic acid desaturation and elongation, which was not significantly influenced by providing gamma-linolenic acid in the diet.

Adult↗

Stereoselective determination of L-amino acids using column liquid chromatography with an enzymatic solid-phase reactor and chemiluminescence detection.

A stereoselective post-column reaction detection system for eight L-amino acids that makes use of a reactor packed with immobilized L-amino acid oxidase is described. The combination of the selectivity of the enzyme and the selectivity of the peroxyoxalate chemiluminescence detection used provides an extremely selective detection system. The detection system gives linear responses over two orders of magnitude and detection limits at the 0.35.10(-6)-3.0.10(-6) M level. The method was used for the determination of selected L-amino acids in urine and beer.

Amino Acids↗

L-type lipase activity in ovaries of superovulated rats. Relation to cholesterol homeostasis.

The impact of lowering the ovarian L(iver)-type lipase activity on cholesterol homeostasis in the ovaries was studied in superovulated rats. L-type lipase activity increased rapidly after injection with chorionic gonadotrophin (HCG) (day 0), its activity remained high between days 3 and 8. During this period plasma progesterone and 20 alpha-hydroxyprogesterone were raised. The ovarian content of unesterified cholesterol remained constant during this period while cholesterol esters increased. Lowering of the L-type lipase activity by in vivo treatment with anti-liver lipase (ALLA) during 4-5 h did not affect plasma hormones or ovarian cholesterol contents. However, de novo cholesterol synthesis in the ovaries was significantly increased by about 40%. After pretreatment of the rats with aminogluthetimide, ALLA administration led to a 250% increase in de novo cholesterol synthesis in the unesterified cholesterol fraction, but was without effect on plasma hormones and on the ovarian cholesterol content. Administration of the cholesterol synthesis inhibitor Simvastatin led to a 25% lowering in ovarian cholesterol synthesis without effect on plasma hormones or ovarian cholesterol content. Additional administration of ALLA affected only the plasma progesterone (-30%). These results indicate that L-type lipase is involved in ovarian cholesterol homeostasis.

Aminoglutethimide↗

Structural modulation of salt-resistant rat-liver lipase alters the relative phospholipase and triacylglycerol hydrolase activities.

This paper demonstrates that structural modification of the heparin-releasable salt-resistant lipase of rat liver (liver lipase) alters its relative capacity to hydrolyze phospholipid and triacylglycerol emulsions. Enzymatic activities were modified by immunoinhibition and proteolysis and by selective amino acid agents. Binding of three different monoclonal antibodies resulted in a lower extent of inhibition of phospholipase than of triacylglycerol hydrolase activity. Degradation of the enzyme by trypsin under mild conditions led to a decrease of both enzyme activities in a different way. Triacylglycerol hydrolase activity was less affected than the phospholipase activity. Visualization of the proteolysis of the purified enzyme by immunoblotting revealed the actual breakdown of a 58 kDa protein into a 53 kDa protein band and subsequently in a 48 kDa one. Incubation of the purified enzyme by N-tosyl-L-phenylethylchloromethyl ketone (acting on cysteine or histidine) or N-ethylmaleimide (a sulfhydryl reagent) did not influence either enzyme activity. On the other hand, after the selective modification of lysine residue(s) by phenylisothiocyanate, the phospholipase A1 activity was stimulated by 68%, whereas the triacylglycerol hydrolase activity was completely lost. The role of a lysine residue(s) in the activity of the enzyme towards phospholipid and triacylglycerol emulsions is discussed.

Animals↗

Progression and regression of human coronary atherosclerosis. The role of lipoproteins, lipases and thyroid hormones in coronary lesion growth.

Relations between lipoprotein fractions, lipoprotein lipase activities, thyroid hormones and coronary lesion growth were studied among 35 male patients with severe coronary atherosclerosis, who had participated in the lipid lowering, dietary Leiden Intervention Trial. Coronary arteriographies were performed at the beginning of the study and 2 years later at termination. The coronary anatomy was quantitated with a computer-based analysis system to assess the progression rate of coronary atherosclerosis on the basis of the absolute arterial dimensions in a patient's coronary tree; for these purposes an absolute coronary score was computed. On the basis of the absolute coronary scores, the entire group of patients could be divided into a no lesion growth group (14 patients) and a progression group (21 patients). Lipoprotein fractions, lipoprotein lipases and thyroid hormones were determined at the end of the trial. No significant difference was found between the no lesion growth and progression groups of patients for total cholesterol (TC) and LDL-cholesterol (LDL-C). The VLDL-cholesterol (VLDL-C) and triglycerides (TG) were significantly higher (P less than 0.05) and HDL-C was almost significantly lower (P less than 0.10) in the progression group. Hepatic lipase (HL) values were significantly higher in the no lesion growth group, as compared to the progression group, whereas lipoprotein lipase (LPL) values were not significantly different. Triiodothyronine (T3) was significantly lower (P less than 0.01) in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions. T3 and HDL were also independently inversely related to coronary atherosclerotic lesion growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiocardiography↗

Effects of synacthen on lipid metabolism in the perfused epididymal fat pad of the rat.

Rats were treated with Synacthen, a synthetic corticotrophin analogue, to induce hypercorticism. The epididymal fat pad was selectively cannulated and perfused. In fasted rats acetone ether powder lipoprotein lipase (LPL) activity rose during treatment to levels found in fed controls. In fed animals no further rise in LPL activity was observed during Synacthen treatment. However, the heparin-elutable LPL activity did not change during this treatment in fasted nor fed animals. Pharmacologic levels of insulin in the perfusion medium caused an increase in heparin-releasable LPL activity as a percentage of total fat pad LPL activity (15% v 48%). Hydrolysis of chylomicrons was higher in fasted three days treated animals then in controls (10 +/- 4% v 2 +/- 2%). In this group a higher uptake of liberated free fatty acids was found (2.6 +/- 1.5% v 1.0 +/- 0.5% in controls). The increase in hydrolysis rate and uptake of fatty acids in the treated fasted animals could not be explained by an increase in releasable LPL activity. Fatty acid release from the fat pad was lower in treated animals than in controls (fasted and fed), basally as well as after adrenalin stimulation. The observation that the epididymal fat pad retains its weight during hypercorticism may therefore be ascribed to an increased influx of fatty acids from increased hydrolysis of TG-rich particles and to an inhibited efflux of fatty acids from the adipocyte. The discrepancy between the LPL activity extractable from an acetone ether powder and the heparin releasable LPL activity suggests impairment of the transport of LPL from the adipocyte to the heparin releasable pool at the endothelium.

Adipose Tissue↗

Surface-free energy and bacterial adhesion. An in vivo study in beagle dogs.

Conflicting reports have been presented on the rôle of substratum surface free energy (s.f.e.) on bacterial adherence. It is the aim of the present study to evaluate the effect of the s.f.e. of substrata on bacterial adherence in vivo. The following substrata with s.f.e. varying from 23.3-124.9 erg X cm-2 were cut into facings of 5 by 6 mm, polished and cleaned: polytetrafluorethylene (PTFE), Parafilm, polyvinylchloride (PVC), polymethylmethacrylate (PMMA), bovine dentin, bovine enamel and glass. In 5 beagle dogs, 7-9 years old, part of the buccal periodontium of the upper cuspids was excised and crowns were made and cemented with a non-fluoridated cement. The facings were placed in the crowns and placed in the oral cavity for 2 h. After removal, the facings were rinsed in saline. S.f.e. was assessed from contact angles with water, water/n-propanol mixtures and a-bromonaphthalene, according to the concept of dispersion and polar components, firstly on clean air dried facings and later on facings exposed to the oral cavity for 2 h. Immediately after rinsing, the water contact angle was measured as a function of time, to monitor the evaporation of free water from the protein layer adsorbed on the substrate which had been exposed to the oral cavity. It appeared that after a rapid increase in contact angle, a stable maximum value was obtained after 40-120 min depending on the substratum. S.f.e.'s of the protein-coated substrata were subsequently determined after a 120 min drying period. Following the contact angle determinations, the exposed facings were stained with ethidium bromide, enabling fluorescence microscopical counting of the adhered microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Disparate effects of ACTH (1-24) and corticosterone on lipoprotein lipase in rat adipose tissue.

The effects of corticosterone and ACTH(1-24) on lipoprotein lipase (LPL) activity of rat epididymal fat tissue were studied. Hypercorticism induced by s.c. administration of 10 mg corticosterone acetate for 3 days led to a decrease in LPL activity. This decrease could be prevented by treatment of the rats simultaneously with synthetic ACTH(1-24). Adrenalectomy also reduced LPL activity. Corticosterone and ACTH(1-24) treatment had a similar effect on LPL activity in adrenalectomized and intact rats. These results indicate that ACTH(1-24) may affect adipose tissue LPL in the rat by a mechanism in which corticosterone is not involved.

Adipose Tissue↗

Effects of doxazosin and propranolol administration on lipoprotein lipases in cholesterol-fed rats.

The effects of alpha 1-adrenergic receptor inhibition with doxazosin, and beta-blockade with propranolol on tissue lipoprotein lipases and plasma lipids were studied in rats. In rats fed a normal lab chow, doxazosin increased heart lipoprotein lipase activity (+14%), while propranolol had the opposite effect (-20%). These effects were not statistically significant when compared with nontreated controls, although the difference between the doxazosin and propranolol groups was significant (p less than 0.05). There were no significant effects on adipose tissue lipoprotein lipase activity or hepatic lipase activity. In rats fed a cholesterol-enriched diet there were similar but smaller effects on heart lipoprotein lipase activity (+5% and -12%, respectively). In these rats alpha 1-inhibition also tended to increase adipose tissue lipoprotein lipase (+14%) and hepatic lipase (+13%), while beta-blockade had the opposite effect (-20% and -9%, respectively). The lipase activities were significantly different between the treatment groups in liver and heart but not in adipose tissue. Doxazosin and propranolol did not affect plasma triglyceride or total cholesterol, but high-density lipoprotein cholesterol was increased during alpha 1-blockade (+24%).

Adipose Tissue↗