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Biomedical subjects

L A Carlson

Publications and source records attributed to L A Carlson.

At least 73 records · Page 4Linked to original sources

Hypertriglyceridemia--acute pancreatitis--ischemic heart disease. A case study in a pair of monozygotic twins.

Hyperlipoproteinemia type V, with serum triglyceride concentrations of about 20 mmol/l, was detected in a pair of monozygotic, 40-year-old twin brothers. One of them had had recurrent attacks of pancreatitis, the other not. The endocrine and exocrine pancreatic functions were apparently normal, supporting that the pancreatitis was secondary to the hypertriglyceridemia. After successful lipid-lowering therapy the attacks of abdominal pain disappeared and remained absent during a 13-year follow-up period. The other twin died of ischemic heart disease nine years after the discovery of his lipid abnormality. The reduction of his lipid levels had been much less successful. His average "atherogenic index" (the ratio of cholesterol in low density to that in high density lipoproteins) was normal but increased to a very high value if cholesterol in very low density lipoproteins was also included together with the low density ones in the numerator. Lipoprotein particles modified in composition may have contributed to an increased uptake through a scavenger pathway and promoted atherosclerosis.

Acute Disease↗

Alpha-lecithin:cholesterol acyltransferase deficiency. Lack of both phospholipase A2 and acyltransferase activities characteristic of high density lipoprotein lecithin:cholesterol acyltransferase in fish eye disease.

The phospholipase A2 and acyltransferase activities characteristic of human plasma lecithin: cholesterol acyltransferase have been evaluated in incubation mixtures of lipoprotein depleted plasma of fish eye disease patients and autologous HDL or homologous normal HDL3. Both enzyme activities were strongly reduced as compared to those of normal controls. These findings further support the claim that fish eye disease plasma has a specific lack of high density lipoprotein lecithin:cholesterol acyltransferase (alpha-LCAT deficiency), although the cholesterol esterification of combined VLDL and LDL in such plasma proceeds at a normal rate.

Acyltransferases↗

Serum cholesterol and cancer--a retrospective case-control study.

The time relationship between low serum cholesterol and the subsequent development of malignant neoplasms was examined in a case-control study of 100 cases of cancer death and 393 controls. The serum cholesterol levels were followed by repeated blood analysis over a 16-year period. An association between low serum cholesterol and cancer death was found particularly for malignant neoplasms of the large intestine and rectum. This relationship diminished 7-16 years prior to death suggesting that the low serum cholesterol levels were an effect of the cancer in an early stage and not vice versa.

Cardiovascular Diseases↗

Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia.

Hyper-alpha-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (beta-VLDL) and triglyceride enrichment of low density lipoproteins (LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin:cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL2 density fraction. The only brother of the patient also had hyper-alpha-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL2. Deficiency of this enzyme activity thus causes accumulation of HDL2 in plasma leading to hyper-alpha-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.

Adult↗

Bile acids and plasma high density lipoproteins: biliary lipid metabolism in fish eye disease.

Cholesterol in plasma high density lipoproteins (HDL) has been proposed to serve as preferential precursor for bile acid biosynthesis in the liver. Furthermore, a negative relationship between plasma levels of HDL cholesterol and biliary saturation with cholesterol has been reported in healthy females. We have performed metabolic studies on a female patient with fish eye disease, a familial condition where plasma HDL levels are reduced by 90% and the concentration of plasma triglycerides is moderately increased. Both the total production of bile acids and the net steroid 'balance' (reflecting total body cholesterol synthesis) were within the range seen in normolipidaemic as well as in hypertriglyceridaemic females. Also the biliary lipid composition and cholesterol saturation of bile were normal. A qualitative abnormality in the bile acid pattern was observed, however, in that the ratio between the synthesis of cholic acid and chenodeoxycholic acid was reduced. It is concluded that a low HDL cholesterol level is not necessarily associated with quantitative abnormalities of biliary lipid metabolism. The abnormal bile acid synthesis ratio may reflect changes in the hepatic precursor pools of cholesterol as the consequence of HDL deficiency, however.

Aged↗

Dyslipoproteinemia in patients with severe bacterial infections.

Infection induces changes in the serum lipoprotein pattern in man. In this report the concentration of cholesterol and triglycerides in the major serum lipoprotein classes were followed in 9 patients with severe bacterial infections. Blood samples for lipoprotein analysis were obtained in the fasting state the first 4 days after admission to the hospital and after 2-3 weeks and 2 months. The serum lipoprotein concentrations of the patients were compared with those from a group of healthy subjects. The total serum cholesterol concentration was lowered during the acute stage of the disease and remained low the first days in hospital. The very low (VLDL) density lipoprotein cholesterol level in serum was mainly within the normal range. The low (LDL) density lipoprotein cholesterol values in serum were low during the first 4 days in hospital. The high (HDL) density lipoprotein cholesterol concentration values were extremely decreased on the first day in hospital and had a tendency to further reduction from day 1 to day 4. Both the LDL and the HDL serum cholesterol were normalized after recovery.

Adult↗

High-density lipoproteins inhibit the bacterial lipopolysaccharide mediated increase in oxidative metabolism and lysozyme release by neutrophilic granulocytes in vitro.

The effects of purified Salmonella endotoxin (LPS) and of LPS combined with isolated human plasma high density lipoproteins (HDL) on oxidative metabolism, measured by nitroblue tetrazolium (NBT)-test, and on lysozyme release of human granulocytes have been studied in vitro. A considerable increase in the NBT-reduction and in lysozyme release was noted in granulocytes exposed to LPS. The stimulating effect of LPS on NBT-reduction and lysozyme release was significantly diminished when the cells were incubated with LPS together with HDL. These observations suggest that HDL in vivo may play an important part in inhibition of metabolic changes induced in granulocytes by LPS which leads to the production and secretion of tissue damaging mediators.

Dose-Response Relationship, Drug↗

Subfractionation and characterization of native and incubation enlarged human plasma high density lipoprotein particles by high performance gel filtration.

Incubation of human plasma in vitro at 37 C results in an increase of the mean particle size of the high density lipoproteins (HDL) accompanied by an almost complete disappearance of the original particles present prior to incubation. A rapid high performance gel filtration technique has been developed in order to study the chemical composition of subfractions of native and incubation enlarged HDL particles as a function of particle size. Subfractionation of HDL isolated by preparative ultracentrifugation from 3 normal human plasmas incubated in vitro at 0 and 37 C for 24 hr have been performed using a 150 cm long TSK-G 3000 SW column. The separation time was less than 65 min. The curves obtained at high performance gel filtration of HDL, by monitoring the effluents from the column at 280 nm, agreed well both in positions of peak maxima and relative peak intensities with the particle distribution patterns observed at polyacrylamide gradient gel electrophoresis of the corresponding HDL preparations run in parallel. The different HDL particle subfractions of the effluents from the gel filtration column have been characterized by quantification of free and esterified cholesterol, total phospholipids and apolipoprotein A-I and A-II. The incubation enlarged HDL particles, subfractionated by the high performance gel filtration technique, were found to have a composition which differed from that of native HDL particles of corresponding size. Incubation enlarged HDL had a generally higher and almost constant relative cholesteryl ester content over the whole particle range compared to native HDL in which a continuous increase in relative cholesteryl ester content could be observed when going from large to small particles. The molar ratio of phospholipids to free cholesterol was higher in small native HDL particles than in the corresponding large ones. The relation between apolipoprotein A-I and A-II remained nearly constant between small and large HDL particles in each subfractionation experiment. The results demonstrate that the high performance gel filtration technique is a rapid and reproducible means for studying the composition of subfractions of HDL particle populations.

Antibodies↗

Concentration and chemical composition of plasma lipoprotein subfractions in patients with peripheral vascular disease. Evidence for normal apolipoprotein B but low cholesteryl ester content in small VLDL.

Subfractionation of the 3 major plasma lipoprotein classes was performed in 20 male patients with symptomatic peripheral vascular disease (PVD) and 18 male healthy controls of similar age and serum lipid levels as the patients in order to investigate if, at comparable levels of total serum lipids, any difference in the distribution or the chemical composition of the lipoprotein subfractions existed between patients and controls. Concentrations of free and esterified cholesterol, triglycerides, phospholipids, apolipoprotein B (apo B) and soluble apolipoproteins did not differ significantly in any lipoprotein subfraction of PVD patients compared to controls. Calculated molecular weights and numbers of lipoprotein particles/ml plasma were also similar in the 2 groups except that there were more heavy LDL particles in the patient group. Plotting concentrations of apo B against cholesteryl ester in the VLDL-D subfraction (Sf 20-100) yielded a linear regression in both groups. The PVD regression line was significantly steeper than that of controls. Calculation of the molecular mass of the various constituents of the VLDL-D fraction in the subjects with the highest content of esterified cholesterol in VLDL-D, where this difference was most pronounced, suggests that this difference was due entirely to a decreased number of cholesteryl ester molecules per lipoprotein particle in PVD. The findings suggest that a disordered metabolism of plasma cholesteryl esters may be present in certain PVD patients.

Aged↗

Genetic and environmental determinants for lipoprotein concentrations in blood.

Path and segregation analyses have been performed on cholesterol and triglyceride contents of serum as well as on very low, low and high density lipoproteins in 78 Swedish nuclear families. The effect of environmental variables like alcohol and smoking on the concentrations of the different lipoproteins has been studied. Genetic heritability was 0.16-0.68 for the cholesterol fractions and 0-0.56 for the triglyceride fractions. No major gene was evident for any of the variables studied.

Adolescent↗

Paradoxical esterification of plasma cholesterol in fish eye disease.

The activity of lecithin: cholesterol acyl transferase (LCAT), the enzyme which catalyses the esterification of human plasma cholesterol, has been measured by two independent methods in plasma from the two known living Swedish patients with fish eye disease. The enzyme activity was in both cases about 15% of that of normal plasma. Paradoxically, however, the percentage of plasma cholesterol which was esterified was almost normal in both patients. In addition, a normal spectrum of the fatty acids of the cholesteryl esters was present indicating a normal cholesterol esterification pathway in vivo. Incubation experiments in vitro of plasma from the two patients also yielded normal cholesterol esterification rates when measured by two different methods. These paradoxical results for cholesterol esterification are discussed on the basis of the present biochemical knowledge of fish eye disease and LCAT deficiency.

Aged↗

Evidence for deficiency of high density lipoprotein lecithin: cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease.

In a rare familial condition, fish eye disease, there is a low relative content of cholesteryl esters in the plasma high density lipoproteins (HDL) but a normal content of these lipids in the very low (VLDL) and low (LDL) density lipoproteins. Lecithin: cholesterol acyltransferase (LCAT) is the enzyme which mediates the esterification of free cholesterol in the plasma lipoproteins. In the present investigation, isolated HDL from our two fish eye disease patients were found to be excellent substrates during in vitro incubations with normal LCAT as present in lipoprotein depleted plasma from control subjects. Almost all free cholesterol of these HDL fractions became esterified and concomitantly the abnormally small fish eye disease HDL particles increased to a size in the range of that of normal HDL particles. Lipoprotein depleted plasma from fish eye disease, however, lacked the property of normal plasma to esterify the free cholesterol of HDL isolated from plasma of fish eye disease patients or control subjects. These results have led to the formulation of a new concept implying that two different LCAT activities exist in normal plasma. One of these activities, denoted alpha-LCAT, is specific for HDL (alpha-lipoproteins) and the other, beta-LCAT, is specific for VLDL-LDL (pre beta- and beta-lipoproteins). Fish eye disease according to this notion is classified as an alpha-LCAT deficiency in contrast to the classical LCAT deficiency which probably lacks both alpha- and beta-LCAT activities.

Aged↗

Evidence for the presence in human plasma of lecithin: cholesterol acyltransferase activity (beta-LCAT) specifically esterifying free cholesterol of combined pre-beta- and beta-lipoproteins. Studies of fish eye disease patients and control subjects.

The present study was undertaken to test our hypothesis that two different lecithin: cholesterol acyltransferase (LCAT) activities exist in normal human plasma, one denoted alpha-LCAT esterifying the free cholesterol of high density lipoproteins (HDL) and the other denoted beta-LCAT acting on the free cholesterol of very low (VLDL) and low (LDL) density lipoproteins. Plasmas depleted of HDL were obtained by means of preparative ultracentrifugation. Incubation at 37 degrees C of these plasma fractions from control subjects and patients with fish eye disease resulted in esterification of the remaining free cholesterol of combined VLDL and LDL (pre-beta- and beta-lipoproteins) in the HDL depleted plasmas. The shapes of the cholesterol esterification rate curves were similar for whole and HDL depleted plasmas from both control subjects and fish eye disease patients. In crosswise mixed incubation experiments with isolated combined VLD and LDL and total lipoprotein depleted plasma from a control subject and a patient with fish eye disease, respectively, esterification of free cholesterol occurred. Incubation of isolated total lipoproteins in plasma from a patient with LCAT deficiency mixed with total lipoprotein depleted plasma from a fish eye disease patient as a source of LCAT caused cholesterol esterification but did not result in normalization of the LCAT deficiency HDL particles, while the amount of normal-sized LDL particles increased. The present results support the hypothesis that a beta-LCAT exists in normal human plasma.

Aged↗

Risk factors for ischaemic heart disease in men and women. Results of the 19-year follow-up of the Stockholm Prospective Study.

In this 19-year follow-up of the Stockholm Prospective Study (SPS), 321 male and 55 female deaths from myocardial infarction (MI) had occurred. Fasting levels of plasma triglycerides acted as an independent risk factor for this cause of death in both sexes, which was the primary question asked when the SPS was designed. Other independent risk factors for MI were for men and women age, systolic blood pressure, smoking and for men only, plasma cholesterol, haemoglobin and erythrocyte sedimentation rate.

Adult↗

Protective effect of nicotinamide against nephropathy in diabetic rats.

Nicotinamide was given for 6 months to rats with streptozotocin induced diabetes. Presence of glomerular depositions (mesangial distribution) of IgG was evaluated with immunofluorescence technique. The immunofluorescence staining of the nicotinamide-treated diabetic rats was significantly less pronounced than that of the untreated diabetic rats. Normal age matched controls showed no such staining. The results indicate that nicotinamide retarded the development of the diabetic nephropathy. The findings might be explained by a normalizing effect of nicotinamide on a disturbed tryptophan and/or nicotinamide adenine dinucleotide metabolism. A metabolic hypothesis is formulated, which is consistent with the "glucose overutilization" theory.

Animals↗