Biomedical subjects

B Christophersen

Publications and source records attributed to B Christophersen.

At least 19 recordsLinked to original sources

PubMed2006

Pancreatitis associated with hyperlipoproteinaemia type I in mink (Mustela vison): earliest detectable changes occur in mitochondria of exocrine cells.

Pancreatic tissue from young mink homozygous for a mutation in the lipoprotein lipase gene was studied by light and electron microscopy, with the aim of describing the earliest detectable changes in a process which rapidly progresses into overt pancreatitis. The mutation leads to hyperlipoproteinaemia, corresponding to hyperlipoproteinaemia type I in man. Assessment of relevant hepatic and pancreatic enzymes were included in the investigation. The earliest detectable changes consisted of widespread swelling and vacuolation of exocrine cells, arising mainly from swollen mitochondria. To a lesser extent, vesiculation of endoplasmic reticulum occurred. Mitochondria exhibited various changes, including cavitation and dilution of the matrix, with shortened and disorganized cristae displaced towards the periphery. Lamellar figures that developed within mitochondria were numerous. Acinar lumina were somewhat dilated, while plasma membranes were relatively well preserved and secretory granules seemed unchanged. Exfoliative processes progressively occurred, resulting in total necrosis of groups of parenchymal cells, while intercalated ducts were spared. The necrosis was rapidly followed by inflammatory reactions. The activity of the mitochondrial enzyme carnitine O-palmitoyltransferase, essential for the transport of fatty acids into the mitochondria, was lower in the pancreas than in the liver. The activity of the peroxisomal fatty acid beta-oxidation was high in the liver and low in the pancreas of both lipoprotein lipase-deficient and control mink. It is concluded that pancreatic lesions associated with hyperlipoproteinaemia start in exocrine cells, and are most probably the result of a metabolic disturbance, possibly a toxic effect of an excess of free fatty acids.

Animals↗

PubMed2001

Serum cholesterol response to replacing butter with a new trans-free margarine in hypercholesterolemic subjects.

UNLABELLED: Margarine leads to lower total and LDL cholesterol (LDL-C) levels than butter but may contain trans fatty acids that increase atherogenic lipids. A food company has used data concerning the cholesterolemic effects of individual fatty acids, including trans fatty acids, to develop a commercially available and virtually trans-free margarine. OBJECTIVE: The effect of this novel margarine on serum lipids and lipoproteins was compared with that of butter in free-living, hypercholesterolemic subjects. DESIGN AND SETTING: A two-period, outpatient cross-over trial at a university hospital lipid clinic. SUBJECTS: The study involved 77 subjects, and was completed by 53 men and 19 women aged 35-65 years with total serum cholesterol levels of between 6.0 and 7.9 mmol/L. INTERVENTION: Two 23-day regimens, separated by a 4-week washout period, included individualised dietary prescriptions supplemented with butter or margarine designed to provide 15% of total dietary energy. RESULTS: In comparison with butter, margarine intake lowered total and LDL-C levels by respectively 11.1% (99% CI: 8.1-14.1) and 11.3% (99% CI: 7.6-15.1). The reduction in LDL-C was < 3% in nearly one-fifth of the subjects despite appropriate changes in serum triglyceride fatty acids. Of the tested clinical and demographic variables, only the percentage of energy obtained from saturated fat during the margarine intake period was associated with dietary responsiveness (explaining 12% of the variation; p < 0.01). CONCLUSION: Our results suggest that a margarine designed to meet nutritional recommendations for hypercholesterolemia is more efficacious than butter in reducing atherogenic lipid levels in hypercholesterolemic subjects.

Adult↗

PubMed2000

Hepatic glucose phosphorylating activities in perch (Perca fluviatilis) after different dietary treatments.

Increased activity of hepatic glucose phosphorylation was observed in perch after feeding previously fasted fish. When a pellet diet containing 14% carbohydrate was given, most of the increased activity had a low affinity towards glucose (S0.5 = 19.5 mM) and resembled the mammalian glucokinase (Hexokinase IV or D) and the glucokinase-like activity previously observed in salmon liver. In addition, increased activity of a hexokinase with high affinity towards glucose (Km = 0.50 mM) was observed with the pellet diet. An increase in the activity of this hexokinase alone was observed when the fish were fed with filet of cod containing less than 0.2% carbohydrate. Perch with a very high hepatic glucokinase-like activity after eating the pellet diet had high activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, indicating a high capacity of glycolysis and carbohydrate utilization. Simultaneously, the activity of glycogen phosphorylase was strongly reduced while the activity of fructose-1,6-bisphosphatase was not significantly changed. These observations were made with perch captured in the spawning season and brought to the laboratory. Assays of glucose phosphorylation in livers of perch eating the natural diet (insects) in the lake showed no glucokinase-like activity.

Animals↗

PubMed1999

Chylomicron metabolism in an animal model for hyperlipoproteinemia type I.

Mink homozygous for the mutation Pro214Leu in lipoprotein lipase (LPL) had only traces of LPL activity but amounts of LPL protein in their tissues similar to those of normal mink. In normal mink, lymph chylomicrons from rats given [3H]retinol (incorporated into retinyl esters, providing a core label) and [14C]oleic acid (incorporated mainly in triglycerides (TG)) were rapidly cleared from the circulation. In the homozygous mink, clearance was much retarded. The ratio of TG to core label in plasma did not decrease and much less [14C]oleic acid appeared in plasma. Still, half of the labeled material disappeared from the circulating blood within 30;-40 min and the calculated total turnover of TG in the hypertriglyceridemic mink was almost as large as in normal mink. The core label was distributed to the same tissues in hypertriglyceridemic mink as in normal mink. Half to two-thirds of the cleared core label was in the liver. The large difference was that in the hypertriglyceridemic mink, TG label (about 40% of the total amount removed) followed the core label to the liver and there was no preferential uptake of TG over core label in adipose or muscle tissue. In normal mink, only small amounts of TG label (<10%) appeared in the liver, while most was in adipose and muscle tissues. Apolipoprotein B-48 dominated in the accumulated TG-rich lipoproteins in blood of hypertriglyceridemic mink, even in fasted animals.

Amino Acid Substitution↗

PubMed1998

Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.

Adult↗

PubMed1998

A mutation in the lipoprotein lipase gene associated with hyperlipoproteinemia type I in mink: studies on lipid and lipase levels in heterozygotes.

Severe hypertriglyceridemia was previously observed in mink. Affected animals had no detectable lipoprotein lipase activity, but normal amounts of lipoprotein lipase protein in post-heparin plasma. We have now cloned cDNA for lipoprotein lipase from normal mink and identified a single point mutation in the affected animals which most likely explains the deficiency of active lipase. The mutation is located in exon 6 and results in a Pro214Leu substitution. In heterozygote mink the levels of lipoprotein lipase activity and mass in post-heparin plasma were lower than in normal mink, but could not be used to identify carriers of the mutation. In some tissues (heart, muscle, kidney and lung), lipoprotein lipase activity was decreased to about 50%. In adipose tissue there seemed to be a mechanism to compensate for the mutation, resulting in increased mass and approximately the same activity of lipoprotein lipase as in animals not carrying the mutation. Mink had high lipoprotein lipase activity and mass in kidneys, although the levels of mRNA in kidney were many fold lower than in adipose tissue. Mink had very low levels of cholesteryl ester transfer protein activity in plasma. This may contribute to the high levels of HDL in this animal species.

Adipose Tissue↗

PubMed1997

[Distress symptoms in hospice patients].

A number of symptoms cause physical or mental distress and suffering in the terminal and dying patient. In this prospective study of 117 patients (96% with a cancer diagnosis) in a Danish hospice all symptoms causing distress were assessed daily in three degrees of severity. The ten most frequently recorded symptoms were: fatigue, pain, weakness, dyspnoea, immobility/paresis, anorexia, general malaise, nausea/vomiting, oedema and amnesia. Fatigue was registered on 60.9% of the admission days, pain on 27.3%, dyspnoea on 19.2% and nausea/vomiting on 8.5%. The prevalence of pain, dyspnoea, nausea/vomiting, thirst and anxiety did not increase during the last seven days of life. Unconsciousness occurred in 23% of the patients during the last 24 hours and in 5% on the day before.

Adult↗

PubMed1997

Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study.

The Scandinavian Simvastatin Survival Study (4S) was a double-blind, randomized placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/l, comprising 4444 patients, equally distributed to a Simvastatin and a placebo group. Patients achieved a significant 30% relative reduction in overall mortality with Simvastatin therapy through a 42% relative reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in Scandinavian coronary heart disease patients were strikingly higher than in healthy controls. Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a) lipoprotein levels, the reduction in deaths being most pronounced in the second (next to lowest) quartile. Subjects with major coronary events had significantly higher Lp(a) lipoprotein levels than subjects without such events, in all groups. The relationship between Lp(a) lipoprotein level and total mortality as well as between Lp(a) lipoprotein level and major coronary events was significantly different from zero, in logistic regression analyses. The findings show that Lp(a) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin. This prospective study provides independent confirmation that a high Lp(a) lipoprotein level is a significant coronary heart disease risk factor.

Adult↗

PubMed1997

HIV dementia and apolipoprotein E.

The effect of apolipoprotein E genotypes on the occurrence of HIV dementia and HIV encephalitis was studied in a sample of 132 AIDS patients in whom clinical data on dementia was available and full autopsy had been performed. There was no statistically significant correlation between risk of HIV dementia or HIV encephalitis in relation to apolipoprotein E genotypes, even after correction for length of survival with AIDS and antiretroviral treatment.

AIDS Dementia Complex↗

PubMed1997

Lipoprotein lipase deficiency with pancreatitis in mink: biochemical characterization and pathology.

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.

Animals↗

PubMed1996

A glucokinase-like-enzyme in the liver of Atlantic salmon (Salmo salar).

An enzyme with properties similar to rat liver glucokinase (Hexokinase IV or D) is present in salmon liver in addition to low-Km hexokinase(s). The specific activity of this enzyme increases about 1.6 fold, comparing activities after feeding diets with 25% and 0% digestive energy from starch. The enzyme has a low affinity for glucose, S0.5 = 25.2-26.8 mM (95% confidence interval) and a low activity with fructose, approximately 8% of the activity with glucose. Its molecular mass was estimated to 50.7 +/- 0.6 kDa (SEM. n = 3) by gel filtration, and it displays positive cooperativity with respect to glucose. The Hill constant = 1.73-1.81 (95% confidence interval). The enzyme is competitively inhibited by N-acetyl glucosamine, K(i) approximately 0.28 mM.

Acetylglucosamine↗

PubMed1996

Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives.

We assessed the relative importance of lipid, apo B, lipoprotein(a) [Lp(a)], and total homocysteine (tHcy) levels in children in relation to premature cardiovascular disease in family members. Parents of 381 girls and 375 boys age 8-12 y completed family history questionnaires. Nonfasting serum lipid and lipoproteins and plasma tHcy and cysteine levels were measured in the children. Serum folate and vitamin B12 levels were determined in a random subsample of 23% of the children, who participated in a food frequency interview. Children whose parents reported hypercholesterolemia had higher total and non-HDL cholesterol and apo B levels than the rest, but these levels were not associated with cardiovascular disease. tHcy levels were similar in girls and boys. tHcy was higher in children whose father, grandfather, or uncle died at age < or = 55 y of myocardial infarction or sudden cardiac arrest (n = 42) than in control children [5.92 mumol/L (95% confidence interval [CI] of 5.47-6.36) versus 5.25 mumol/L (95% CI, 5.16-5.34)], also after adjustment for socioeconomic group. Intake and serum levels of vitamin B12 and folate were within recommended or reference ranges. In a stepwise multiple regression analysis, serum folate (negative correlation), plasma creatinine, and sugar intake as percent of dietary energy (positive correlations) were significantly associated with tHcy (multiple r = 0.44, adjusted r2 = 18%; 95% CI, 5-30%). Our data show that a modest elevation in tHcy in children was related to premature cardiovascular death in their male relatives and may partly account for the contribution of family history to risk of cardiovascular disease. tHcy may be modifiable through the diet, even in children with apparently adequate vitamin nutriture.

Age of Onset↗

PubMed1995

[A rapid analysis of the lipid profile. A comparative study of different analytical methods for determination of blood lipids].

A simple and rapid analytical assay for determination of total cholesterol, HDL-cholesterol and triglycerides in capillary blood samples has been compared with established laboratory methods in a group of 41 test subjects. The new method produces results that are fully acceptable for determination of these three lipid parameters, and agree well with the results obtained in serum by established laboratory methods. The Cholestech LDX analyser may be useful for providing rapid and accurate measurements of the lipid profile, including total cholesterol, triglycerides and HDL-cholesterol. Its small size, the speed of analysis and the fact that it is easy to use make the Cholestech LDX a suitable instrument for use in out-patient clinics and primary care medicine.

Blood Chemical Analysis↗

PubMed1993

[Apolipoprotein E phenotyping--useful in the study of hyperlipoproteinemia type III].

Apolipoprotein E (apo E) is a protein constituent of several plasma lipoproteins. Its major physiological role is to mediate the interaction of these lipoproteins and receptors. Three common apo E alleles and six phenotypes are known. The phenotype E2/E2 is associated with type III hyperlipoproteinemia. As a consequence of the increasing clinical interest in apo E phenotypes, especially in relation to the diagnosis of type III hyperlipoproteinemia, we have established a method for apo E phenotyping. Allele frequencies from a population of 211 healthy individuals are presented. The results show that, like as in Finland and Sweden the e4 allele is more frequent than in non-Nordic countries.

Adult↗

PubMed1991

The effect of n-3 fatty acids on osmotic fragility of rat erythrocytes.

In order to study the effect of n-3 fatty acids on the physical state of the erythrocyte membrane, measured as osmotic fragility, rats were fed a diet supplemented in n-3 fatty acids (1.5 ml/day, 35% 20:5, 30% 22:6) for 21 days. With salt concentrations ranging from 0.37% to 0.44%, osmotic resistance was increased by 25% to 45% in cells from n-3-fed animals compared to controls. No change was observed in either phospholipid or cholesterol content in the membrane. A small, but still significant difference (P less than 0.05) in phospholipid sub-class distribution was observed in that the phosphatidylethanolamine fraction was decreased and the phosphatidylserine fraction increased after n-3 supplementation. The major change was, however, that the level of eicosapentaenoic acid (20:5(n-3] in phospholipids was increased from 1.5% of total fatty acids to 4.5%. This increase was mainly at the expense of linoleic acid (18:2(n-6]. No change was observed in the level of docosahexaenoic acid (22:6(n-3]. It is thus concluded that both the fatty acid composition and the nature of the phospholipid polar head group may influence the osmotic fragility of erythrocytes.

Animals↗

PubMed1991

Liver steatosis in hypobetalipoproteinemia. A case report.

A case of hypobetalipoproteinemia is described; a 16-year-old girl had been suffering for nearly 2 years from diffuse abdominal pain. The only clinical features were liver steatosis, slightly increased amino transferases and an incipient polyneuropathy. No sign of malabsorption or gastrointestinal disease was found. She had extremely low levels of cholesterol and triacylglycerol in her serum, slightly decreased serum phospholipids and normal HDL-cholesterol levels. Apolipoprotein B-100 was approx. 8% of normal, whereas B-48 was present at essentially normal levels. Electron microscopy of lipoprotein particles showed normal morphology of LDL. Examination of close relatives showed no abnormalities. Southern blots revealed no major deletions or rearrangements at the genomic level. Although rare, a- and hypobetalipoproteinemia should be considered as possible etiologies in patients with unexplained steatosis in the liver.

Adolescent↗

PubMed1991

Insulin and glucagon family peptides in relation to activities of hepatic hexokinase and other enzymes in fed and starved Atlantic salmon (Salmo salar) and cod (Gadus morhua).

1. Plasma levels of insulin, glucagon, and glucagon-like peptide (Glp) were all reduced by starvation of salmon and cod. In the salmon the drop in Glp was larger than in insulin and glucagon. 2. After starvation the activity of hexokinase (EC 2.7.1.1) was increased in salmon liver, but decreased in cod liver. The salmon hepatic hexokinase activity was inversely correlated with the Glp/insulin ratio. 3. Activities of hepatic glycogen phosphorylase (EC 2.4.1.1) and phosphofructokinase (EC 2.7.1.11) were increased in starved as compared to fed salmon. In cod, starvation resulted in decreased or unchanged activity of phosphorylase. This discrepancy may be related to different degrees of environmental and handling stress. 4. Intraperitoneal injection of human insulin in salmon gave increased hepatic phosphorylase and hexokinase activities and reduced plasma levels of glucagon, Glp and endogenous fish insulin at sampling after 30 hr. 5. No differences in hepatic hexokinase activities or plasma hormone levels were observed between cod fed low and high carbohydrate diets. Apparently, regulation of glucose phosphorylation by dietary carbohydrate does not occur.

Animals↗

PubMed1991

Glucose dehydrogenase, glucose-6-phosphate dehydrogenase and hexokinase in liver of rainbow trout (Salmo gairdneri). Effects of starvation and temperature variations.

1. Activities of trout liver glucose dehydrogenase (GDH, EC 1.1.1.47) and glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) were increased after a sudden drop in water temperature, but not in long-time cold acclimated as compared with warm acclimated trout. 2. Possibly, the activities of GDH and G6PD were temporarily increased in connection with metabolic adaptation to the lower temperature. 3. The activities of GDH and G6PD were not changed by the stress of handling. 4. Partially purified trout liver GDH has a lower activation energy with glucose than with glucose-6-phosphate as substrate, and the Km (glucose) decreases with decreasing assay temperature. 5. At low temperatures, the activity of trout liver GDH with glucose as substrate may be comparable to that of glucose-6-phosphate. 6. Partially purified beef liver GDH has a high activation energy with glucose as substrate, and the Km (glucose) does not change with the assay temperature. 7. Hexokinase (HK, EC 2.7.1.1) and GDH activities were unchanged when trout were deprived of food for 4 weeks. Apparently, the trout liver glucose utilization did not adapt to the starvation.

Acclimatization↗