Transplacental amino acid transfer and its study using positron emission tomography. A short review based on a doctoral thesis.
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Amino Acids↗
Biomedical subjects
L Berglund
Publications and source records attributed to L Berglund.
Hypocholesterolaemia and increased elimination of low-density lipoproteins in metastatic cancer of the prostate.
To study the influence of tumour mass on lipid metabolism, the lipoprotein pattern in untreated patients with newly diagnosed cancer of the prostate was examined. Total cholesterol levels were reduced in patients with evidence of metastasis (n = 30) compared with those without metastasis (n = 73). Since the major fraction of serum cholesterol is contained in low-density lipoproteins (LDL), turnover of LDL was studied in detail in 8 patients compared with 12 age-matched healthy men. LDL were cleared faster in the 3 patients with metastatic disease than in the patients without metastasis and in controls, indicating faster catabolism of LDL. Thus in prostatic cancer an increased tumour burden is associated with increased elimination of LDL, which contributes to reduced serum cholesterol levels.
Aged↗
[New pharmaceuticals for patients with atherosclerosis are under development. Antioxidants inhibit LDL modification].
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Antioxidants↗
Tin-protoporphyrin and long wave length ultraviolet light in treatment of psoriasis.
To assess the effects of tin (Sn)-protoporphyrin (a synthetic haem analogue) in conjunction with long wave length ultraviolet light (UVA) radiation in psoriasis 10 patients, 9 of whom were substantially or completely unresponsive to other forms of therapy, received 2.0 mumol/kg bodyweight of Sn-protoporphyrin for 1 day followed by UVA light treatment for 21 days. The average starting UVA dose was 5.6 (SD 2.0) J/cm2, and the average cumulative UVA dose was 98.3 (35.1) J/cm2. Severity of psoriatic plaques, scored clinically on a scale of 0-3 for erythema, scaling, and induration, fell from a mean score of 7.9 at the start of the study to 3.6 at the end. Psoriatic lesions were improved in all patients and the effect was striking in some. The responses lasted throughout the three weeks of the study and no deleterious side-effects of the treatment were noted. Clinical follow-up for three months showed no rebound in disease activity. Sn-protoporphyrin with conventional UVA light may be useful in the treatment of psoriasis.
Adult↗
Activation of rat liver cytosolic phosphatidic acid phosphatase by nucleoside diphosphates.
Phosphatidic acid phosphatase (EC 3.1.3.4) was purified 30-fold by ammonium sulfate fractionation and hydroxyapatite chromatography from the soluble fraction of rat liver. ADP was found to stimulate the enzyme activity with half-maximal stimulation at 0.2 mM. Similar effects were seen when ADP was replaced by GDP or CDP. In contrast, ATP inhibited the enzyme; half-maximal inhibition observed at 0.2 mM. Again, the degree of inhibition did not differ when GTP or CTP replaced ATP. Thus, the structure of the base part of the nucleotide was not critical for mediating these effects. The positions of the phosphate groups in the nucleotide structure were however found to be of importance for the enzyme activity. Variations in the structure of the phosphate ester bound at the 5'-position had a pronounced effect on phosphatidic acid phosphatase activity. The effect of nucleotides depended on pH, and the inhibition by ATP was more pronounced at pH levels lower than 7.0, whereas the stimulatory effect of ADP was virtually the same from pH 6.0 to pH 8.0. The enzyme showed substrate saturation kinetics with respect to phosphatidic acid, with an apparent Km of 0.7 mM. Km increased in the presence of ATP, whereas both apparent Vmax and Km increased in the presence of ADP, suggesting different mechanisms for the action of the two types of nucleotides. The results indicated that physiological levels of nucleotides with a diphosphate or a triphosphate ester bound at the 5'-position of the ribose moiety influenced the activity of phosphatidic acid phosphatase. The possibility is discussed that these effects might be of importance for the regulation of triacylglycerol biosynthesis.
Adenosine Diphosphate↗
Oestrogen-induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit.
Administration of moderate pharmacological doses of oestrogen to cholesterol-fed rabbits for 12 weeks resulted in a dramatically retarded development of arterial lesions as compared to non-oestrogen-treated, cholesterol-fed rabbits (7% vs. 47% aortal involvement). Oestrogen treatment was associated with a retarded increase in plasma cholesterol, and five times higher high density lipoprotein (HDL) to very low density lipoprotein (VLDL) cholesterol ratio. Expression of hepatic lipoprotein receptor activity, as detected by heparin-releasable binding of 125I-hypercholesterolaemic VLDL, was heavily suppressed by cholesterol feeding. Administration of oestrogen modulated this response and resulted in higher receptor expression. In accordance, oestrogen treatment resulted in a less prominent reduction of 125I-hypercholesterolaemic VLDL clearance in the cholesterol-fed rabbits. VLDL from both groups of cholesterol-fed animals stimulated cholesteryl ester synthesis in cultured macrophages to the same extent. Thus, in rabbits under a dietary cholesterol load, oestrogen counteracted hepatic lipoprotein receptor suppression, reduced plasma VLDL- and increased plasma HDL-cholesterol levels, and to a large extent abolished the development of atherosclerosis.
Animals↗
Lipid lowering in severe familial hypercholesterolaemia: efficacy and safety of a new regenerating system for selective apheresis of apolipoprotein B-containing lipoproteins.
Preliminary experience of the efficacy and safety of a new regenerating system for selective extracorporeal removal of apolipoprotein B-containing lipoproteins is described. Four patients with familial hyperlipoproteinaemia were studied on 10 occasions. A system of two, parallel, dextran sulphate cellulose columns was used, and plasma was processed continuously by passage through one of the columns while the other was being regenerated. With this procedure, reductions of very low density and low density lipoprotein cholesterol levels by 73 and 43%, respectively, could be achieved after treatment for 2.5-3 h (1000-3200 ml of plasma volume). No clinically relevant changes in the concentrations of other plasma proteins, including high density lipoproteins, were observed, and the treatment was well tolerated. We conclude that continuous selective apolipoprotein B apheresis is a safe and efficient lipid-lowering procedure which may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.
Apolipoproteins B↗
Early determination of serum lipids and apolipoproteins in acute myocardial infarction: possibility for immediate intervention.
Early identification of elevated cholesterol in patients with acute myocardial infarction (MI) is of interest as secondary prevention can then be initiated when patients are highly motivated. However, since the lipid pattern changes during acute MI, screening for lipid disturbances is often not performed until 6 months later. We prospectively studied lipid and apolipoprotein levels during acute MI and 3 and 6 months later in 123 consecutive acute MI patients, mean age 64 +/- 10 (SD) years, who were admitted within 24 h from onset of symptoms, mean delay 5.5 h. Blood was taken at admission to the Coronary Care Unit (CCU), the first morning in the CCU, at hospital discharge and at 3 and 6 months follow-up. Patients were fasted overnight except at admission, and no specific dietary advice was given. Total serum cholesterol, triglycerides, and apolipoprotein (apo) A-I concentrations did not differ significantly (1-3%) between CCU admission and the 3 and 6 months control. During the subsequent hospital period, lipid concentrations generally decreased and at discharge were 15-25% below those at 6 months follow-up (P less than 0.001). The highest correlations between immediate CCU determination and 6 months follow-up were obtained for cholesterol (r = +0.71) and apo B (r = +0.67). Thus, lipid levels obtained early at CCU admission in acute MI patients are representative of the patient's baseline levels which are in contrast to those registered later during hospital stay. This information could be used to identify patients for early intervention.
Adult↗
Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma.
To characterize the effects of estrogen treatment on the metabolism of LDL we studied six males with metastatic prostatic carcinoma before and during the initiation of therapy; a repeated study was performed in five participants after 3-6 mo of treatment. The fractional catabolic rate (FCR) of autologous 125I-LDL was calculated both from elimination curves of plasma radioactivity and from urine/plasma (U/P) radioactivity ratios. Within 1-2 d of onset of estrogen therapy a more rapid decay of plasma radioactivity occurred, and FCR measured from U/P ratios increased by 20%. Concomitantly, LDL cholesterol levels decreased by 16%. After 3-6 mo of treatment FCR determined by both techniques was almost doubled, and LDL cholesterol was reduced by 34%. This occurred despite a 29% increase in the calculated synthesis rate of LDL. Tissue culture studies demonstrated that the receptor affinity of LDL isolated from patients on long-term estrogen therapy was reduced. We conclude that a profound increase in LDL catabolism is induced through administration of pharmacological doses of estrogen in males, and hypothesize that this is the consequence of an increased expression of hepatic LDL receptors. This enhanced catabolism of LDL leaves LDL particles in plasma with lower affinity for the LDL receptor.
Aged↗
Breech extraction versus cesarean section for the remaining second twin.
All second twins delivered by cesarean section (CS) after vaginal birth of the first twin (n = 38) and all breech-extracted second twins (n = 282) in Sweden during 1973-81 were identified. Data from the medical records of all CS second twins were extracted and compared with breech-extracted second twins from the same departments born within 2 years of the CS twin (n = 25). Second twins delivered after maternal general anesthesia had lower 5-min Apgar scores, irrespective of mode of delivery. Maternal morbidity was substantial in the CS group. The results encourage the use of breech extraction under local anesthesia rather than CS when there is a need for a quick delivery of the second twin and when both alternatives are available.
Anesthesia, Obstetrical↗
Heterophilic antibodies against rabbit serum causing falsely elevated gonadotropin levels.
Two cases are presented in which previously acquired antibodies against rabbits in the patient's serum caused falsely elevated hormonal levels in radio-immuno assays (RIA) based on rabbit antibodies to follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). The erroneous results led to unnecessary operative intervention and inconvenience for the patients.
Adult↗
Rat adipose tissue phosphatidic acid phosphatase: lack of effect of nucleotides on cytosolic enzyme activity.
The soluble phosphatidic acid phosphatase from rat adipose tissue was partially purified using ammonium sulfate fractionation and hydroxyapatite chromatography. Administration of ethanol has been found to increase phosphatidic acid phosphatase activity. The enzyme activity has been found to be dependent on magnesium ions with maximal activity at 2-5 mM magnesium. The enzyme displays an apparent pH optimum of 7.0. The activity of the enzyme is not affected by addition of ATP or ADP, in contrast with the results for hepatic phosphatidic acid phosphatase. The results suggest that these two enzymes may be regulated by different mechanisms and that they may thus represent two different types of isoenzyme.
Adenosine Diphosphate↗
Treatment of psoriasis vulgaris with a synthetic metalloporphyrin and UVA light.
Sn-protoporphyrin is a synthetic heme analogue which inhibits the catabolism of natural heme to bilirubin and can suppress a wide variety of experimentally induced or naturally occurring forms of jaundice in animals and man. Ten patients, 9 of whom were substantially or completely unresponsive to other forms of therapy, received 2.0 mumol/kg body weight of Sn-protoporphyrin on day 0 of this study followed by UVA light treatment for 21 days. Severity of psoriatic plaques, clinically scored (erythema 0-3; scaling, 0-3; infiltration, 0-3;) declined from a mean +/- score of 7 +/- 0.3 on day 0 to 3.6 +/- 0.7 on day 21. Psoriatic lesions were improved in all patients and in some the effect was dramatic. No deleterious side effects were registered. As shown in this study, one-day treatment with Sn-protoporphyrin followed by conventional UVA light treatment may be a useful therapeutic modality for psoriasis patients and merits further investigation.
Adult↗
Effects of lovastatin therapy on guinea pig low density lipoprotein composition and metabolism.
Lovastatin therapy is known to induce hepatic low density lipoprotein (LDL) receptor mRNA and LDL receptor activity. Yet, in studies in humans and animals it has been difficult to demonstrate an enhancement of the plasma fractional catabolic rate (FCR) of an injected LDL tracer during lovastatin therapy. One explanation may be that the composition of the LDL tracer may also change during therapy, independently affecting LDL clearance. To test this possibility we fed guinea pigs lovastatin, which led to a decrease in their plasma LDL cholesterol levels. Composition studies showed that LDL isolated from lovastatin-treated guinea pigs was slightly cholesterol-depleted and triglyceride-enriched when compared to LDL isolated from control animals. Several independent lines of investigation documented that a substantial increase in hepatic LDL receptor activity occurred in response to the lovastatin treatment. Consistent with this, when a single LDL tracer was injected into control and lovastatin-treated guinea pigs, the FCR was always more rapid in the lovastatin-treated animals. However, when LDL isolated from lovastatin-treated animals (L-LDL) was simultaneously injected intravenously with LDL isolated from control animals (C-LDL) the FCR of the C-LDL was always more rapid than that of the L-LDL. When one compared the FCR of C-LDL determined in control animals with the FCR of L-LDL determined in lovastatin animals there was no difference. Possible explanations for these paradoxical findings are discussed.
Animals↗
Stimulatory effect of mevinolin on rat liver phosphatidic acid phosphatase.
The activity of the soluble form of phosphatidic acid phosphatase in rat liver was stimulated about 2.5-fold by inclusion of mevinolin, a competitive hydroxymethylglutaryl-CoA reductase inhibitor, in the diet (0.1%). The stimulatory effect of mevinolin was present also after dietary addition of cholestyramine (5%) or intraperitoneal administration of ethanol. Addition of cholesterol (2%) to the diet totally abolished the stimulation by mevinolin on phosphatidic acid phosphatase. The results support a correlation between the synthesis of the rate-limiting enzyme in cholesterol biosynthesis and the activity of the apparent rate-limiting enzyme in triacylglycerol biosynthesis.
Acid Phosphatase↗
Plasma exchange in a patient with heterozygous familial hypercholesterolaemia resistant to drug therapy.
A 40-year-old male with heterozygous familial hypercholesterolaemia was resistant to combined drug treatment with cholestyramine and nicotinic acid in adequate doses. He had angina pectoris and evidence of three vessel disease in the coronary angiogram. Repeated plasma exchange at intervals of 1-3 weeks simultaneously with combined drug treatment decreased the plasma cholesterol levels by nearly 40%. There were also signs of regression of xanthomata and some improvement of his angina pectoris. No progression of atherosclerosis was seen angiographically after two years treatment. Plasma exchange may be a therapeutic alternative in drug-resistant familial hypercholesterolaemia.
Adult↗
[Raw spiced fish as an indirect cause of severe anemia and weight loss].
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Adult↗
Evidence against in vitro modulation of rat liver cholesterol 7 alpha-hydroxylase activity by phosphorylation-dephosphorylation: comparison with hydroxymethylglutaryl CoA reductase.
The activity of cholesterol 7 alpha-hydroxylase in rat liver microsomes was investigated under conditions favourable for phosphorylation-dephosphorylation. The enzyme activity was similar in the presence or absence of sodium fluoride during preparation. Preincubation with ATP and magnesium did not affect the enzyme activity. Cholesterol 7 alpha-hydroxylase was inhibited by alkaline phosphatase, but this inhibition was similar also after inactivation of the phosphatase. Under similar conditions, rat hepatic hydroxymethylglutaryl CoA reductase activity was clearly modulated in agreement with phosphorylation-dephosphorylation. The absence of such a modulation of cholesterol 7 alpha-hydroxylase argues against involvement of phosphorylation-dephosphorylation in the regulation of this enzyme.
Animals↗