Biomedical subjects

L Holmquist

Publications and source records attributed to L Holmquist.

At least 55 records · Page 3Linked to original sources

PubMed1988

Effects of nicotinic acid on concentrations of serum apolipoproteins B, C-I, C-II, C-III and E in hyperlipidemic patients.

Twenty-four patients with Type IIa, IIb, III and IV hyperlipoproteinemia (HLP) were treated with 4 g of nicotinic acid daily with the purpose to study its effect on serum apolipoprotein B, C-I, C-II, C-III and E concentrations. Triglyceride and total cholesterol concentrations of whole serum and of different serum lipoprotein fractions were also determined. Analyses were performed prior to and after a drug treatment period of 6 weeks, during which all the patients were weight stable. Treatment caused a decrease in serum concentrations of apolipoproteins C-I, C-II, C-III and E. These highly significant reductions were all positively correlated to a reduction of very low density lipoprotein triglyceride levels of serum (r-values greater than 0.76, p less than 0.001). There were highly significant decreases in serum levels of apolipoprotein B and low density lipoprotein total cholesterol. These reductions were positively intercorrelated (r = 0.55; p less than 0.01). Similar effects were observed in the different HLP types and in both sexes. Treatment resulted in normolipidemia in 12 patients, who were hypercholesterolemic (7 type IIa, 3 type IIb, 2 type III hyperlipoproteinemia) prior to treatment. The serum apolipoprotein B concentrations of these 12 patients fell after therapy to values which, however, remained abnormally high. We suggest that serum lipid adjusting treatment should aim at a normalization not only of serum lipid concentrations but also of the serum apolipoprotein B concentration in order to achieve a maximal antiatherogenic effect.

Adult↗

PubMed1988

The diagnostic value of colonoscopy compared with rectosigmoidoscopy in children and adolescents with symptoms of chronic inflammatory bowel disease of the colon.

Seventy-eight young patients with symptoms of chronic inflammatory bowel disease (IBD) of the colon have been investigated to determine to what degree colonoscopy adds important information for the diagnosis of IBD in addition to results of the routine procedures, including rectosigmoidoscopy carried out at the same time. After colonoscopy IBD was established in 4 of 12 patients classified as non-IBD after the routine procedures. Eleven of 18 patients with the routine diagnosis indeterminate colitis (IC) could after colonoscopy be differentiated into UC or probable CC. In 30 of 31 cases classified as UC the routine diagnosis was confirmed by colonoscopy. Routine diagnosis as probable CC was changed to definite CC in 3 of 10 cases. In all cases but one with previously established IBD it was possible to confirm the diagnosis. Thirty-seven of 70 patients with established IBD of the colon had no radiologic evidence of colitis.

Adolescent↗

PubMed1988

Lipoprotein metabolism in hepatic lipase deficiency: studies on the turnover of apolipoprotein B and on the effect of hepatic lipase on high density lipoprotein.

Hepatic lipase deficiency produces significant distortion in the plasma lipoprotein profile. Particles with reduced electrophoretic mobility appear in very low density lipoprotein (VLDL). Intermediate density lipoprotein (IDL) increases markedly in the circulation and plasma low density lipoprotein (LDL) levels fall. At the same time there is a mass redistribution within the high density lipoprotein (HDL) spectrum leading to dominance in the less dense HDL2 subfraction. The present study examines apolipoprotein B turnover in a patient with hepatic lipase deficiency. The metabolism of large and small very low density lipoproteins was determined in four control subjects and compared to the pattern seen in the patient. Absence of the enzyme did not affect the rate at which large very low density lipoproteins were converted to smaller particles within this density interval (i.e., of VLDL). However, subsequent transfer of small very low density lipoproteins to intermediate density particles was retarded by 50%, explaining the abnormal accumulation of VLDL in the patient's plasma. Despite this, intermediate density particles accumulated to a level 2.4-times normal because their subsequent conversion to low density lipoprotein has been almost totally inhibited. Consequently, the plasma concentration of low density lipoprotein was only 10% of normal. On the basis of these observations, hepatic lipase appears to be essential for the conversion of small very low density and intermediate density particles to low density lipoproteins. The pathways of direct plasma catabolism of these species were not affected by the enzyme defect. In vitro studies were performed by adding purified hepatic lipase to the patient's plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

The isolation and characterisation of a cDNA clone for human lecithin:cholesterol acyl transferase and its use to analyse the genes in patients with LCAT deficiency and fish eye disease.

We have isolated cDNA clones coding for human lecithin:cholesterol acyl transferase (LCAT) from a liver-specific cDNA library by the use of two oligonucleotide probes based on the protein sequence. The clones span the sequence coding for the entire secreted LCAT, the 3' untranslated sequence and 12 amino acids of the signal peptide. The peptide sequence contains the conserved active site of serine lipases within a hydrophobic domain, flanked by a possible amphipatic alpha-helix. Only one gene for LCAT could be detected in genomic blots. We have used the cDNA as a probe to analyse the LCAT gene in patients suffering from LCAT deficiency and fish eye disease. No rearrangements or abnormal gene fragments were detected in these patients.

Amino Acid Sequence↗

PubMed1987

Net lipid transfer between lipoproteins in fish-eye disease plasma supplemented with normal high density lipoproteins.

Native fish-eye disease plasma, which is deficient of both high density lipoproteins (HDL) and lecithin-cholesterol acyltransferase activity (alpha-LCAT), processing the free cholesterol of these lipoproteins, has been supplemented with normal isolated HDL2 or HDL3 and incubated in vitro at 37 C. After incubation for 0, 7.5 and 24 hr the very low density (VLDL) and low density (LDL) lipoproteins as well as HDL were isolated, and their contents of triglycerides, phospholipids and free, esterified and total cholesterol were quantified. The resulting net mass transfer of the different lipids revealed a functioning transfer of cholesteryl esters and all other analyzed lipids between the lipoproteins, although no de novo esterification of the HDL cholesterol by LCAT in this plasma occurred. In accordance with previous findings there was a functioning esterification process of the free cholesterol of the combined VLDL and LDL of fish-eye disease plasma. The present reports make it reasonable to conclude that the lack of HDL cholesterol esterification in this disease is not a result of a deficiency of cholesteryl ester transfer or lipid transfer activities.

Cholesterol↗

PubMed1987

Increased removal rate of exogenous triglycerides after prolonged exercise in man: time course and effect of exercise duration.

Ten healthy young men exercised for 1.5 and 3 hours, respectively, 4 to 6 weeks apart at the same work intensity, corresponding to 77% of the individual maximal heart rate. In the fasting state 1 mL of 10% Intralipid/kg body weight was injected IV, the fractional removal rate was calculated (k2-value), and fasting lipid and apolipoprotein C-I, C-II, and CIII concentrations were determined one day before, immediately before, immediately after, and one day after the exercise: measurements were also made two and three days after the three-hour session. An increase of the k2-value was found only the day after the three-hour exercise (+66%, P less than .01), while after the 1.5-hour exercise the k2-value was not changed. One and two days after the three-hour exercise the fasting serum triglyceride concentration was significantly decreased by 33% and 16%, respectively. Serum triglyceride concentration was decreased also the day after the shorter session (-17%, P less than .05). Decreases in serum cholesterol concentrations were significant after both exercise bouts, but the significance disappeared if corrections for the changes in calculated plasma volume were made. Serum level of C apolipoproteins was decreased one day after the three-hour exercise, while it was not changed after the shorter exercise. This study shows that prolonged exercise produces an increase in the removal rate of Intralipid triglycerides from the bloodstream, that this change is related to the duration of exercise, and that some time is required following the exercise, before it is manifest.

Adult↗

PubMed1987

Purification of human plasma lecithin:cholesterol acyltransferase by covalent chromatography.

Human plasma lecithin:cholesterol acyltransferase (LCAT, EC 2.3.1.43) has been purified more than 20,000 fold from plasma in 10% yield. This new procedure is composed of only four steps, including ultracentrifugation of plasma to yield a 1.21-1.25 kg/l density fraction, covalent binding of LCAT in this fraction to thiopropyl-Sepharose followed by adsorption of the enzyme to wheat-germ lectin-Sepharose for elimination of albumin and finally batch-wise treatment of the desorbed LCAT with hydroxyapatite to remove residual impurities. The purified enzyme was free of apolipoprotein A-I, A-II, B, C-I, C-II, C-III and E as checked by double immunodiffusion and SDS-electrophoresis, which latter method also demonstrated the absence of hitherto characterized lipid transfer proteins. Only traces of apolipoprotein D were present in the preparation as detected by immunoblotting. The purified enzyme retained alpha- and beta-LCAT activities. Non-denaturing and denaturing polyacrylamide gel electrophoresis yielded apparent molecular masses of 69 and 66 kDa, respectively, for the enzyme which on isoelectric focusing produced one major and one minor isoform with pI values of 4.20 and 4.25, respectively. Apolipoprotein A-I was required to transform artificial lecithin-cholesterol liposomes into substrates for the purified LCAT.

Chromatography↗

PubMed1987

In vitro normalization of cholesteryl ester content and particle size of fish eye disease high density lipoproteins.

Isolated high density lipoprotein (HDL) from the two living fish eye disease patients have been incubated in vitro with autologous lipoprotein depleted plasma or with lipoprotein depleted plasma from domestic pig (Sus domesticus), with and without the presence of LCAT inhibitor for 24 hours at 0 and 37 degrees C. The lecithin:cholesterol acyltransferase (LCAT) activity in lipoprotein depleted pig plasma increased the abnormally low cholesteryl ester content of the fish eye disease HDL particles from about 20 to 100% and increased their exceptionally small mean particle size, probably by particle fusion, to a range which is representative of normal HDL3. Both esterification and particle enlargement were totally blocked by the LCAT inhibitor. Incubation of concentrated fish eye disease HDL with autologous lipoprotein depleted plasma for 24 hours at 37 degrees C resulted in a small increase in its cholesteryl ester percentage to 37%, without affecting the apparent HDL particle size. This finding confirms a deficiency of HDL lecithin:cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease. The observed normalization of both HDL cholesteryl ester percentage and particle size by lipoprotein depleted pig plasma which contains virtually no cholesteryl ester transfer activity indicates that the latter is not a requisite for esterification of the free cholesterol of fish eye disease HDL.

Animals↗

PubMed1987

Inhibitory effect of normal high density lipoproteins on lecithin:cholesterol acyltransferase activity in fish eye disease plasma.

The lecithin:cholesterol acyltransferase (LCAT) activity of lipoprotein depleted normal and fish eye disease (FED) plasma was assayed in a modified Glomset-Wright incubation system where the enzyme was allowed to act on three different normal lipoprotein substrates consisting of an authentic mixture of very low (VLDL), low (LDL) and high (HDL) density lipoproteins to assay total LCAT activity, HDL to assay alpha-LCAT activity and combined VLDL and LDL to assay beta-LCAT activity, respectively. However, using normal plasma depleted of HDL, leaving its combined VLDL and LDL as enzyme substrate, resulted in a more than twofold increase in the LCAT activity of FED plasma from the two patients compared to the activity obtained with HDL present in the incubation mixture, indicating an inhibitory effect of HDL on the beta-LCAT activity present in FED plasma. This inhibitory effect of normal HDL could also be demonstrated by autoincubation of FED plasma mixed with isolated HDL2 or HDL3. Both these HDL subfractions had a pronounced inhibitory effect on the cholesteryl ester formation in FED plasma. The present study thus clearly demonstrates that normal HDL inhibits the beta-LCAT activity present in FED plasma, esterifying the free cholesterol of combined VLDL and LDL, derived from controls as well as from the two FED patients.

Corneal Opacity↗

PubMed1987

Different substrate specificities of plasma lecithin: cholesterol acyl transferase in fish eye disease and Tangier disease.

Esterification of plasma free cholesterol is mediated by lecithin:cholesterol acyl transferase (LCAT). The free cholesterol of plasma high density lipoproteins (HDL) is considered to be the preferred substrate for LCAT. It therefore appeared as a paradox that plasma cholesterol esterification, both in vivo and in vitro, is normal in fish eye disease and Tangier disease, two familial conditions with extremely low plasma HDL levels. Fish eye disease plasma, however, was shown to have LCAT activity primarily acting on combined very low (VLDL) and low (LDL) density lipoproteins, denominated beta-LCAT, while it lacked LCAT activity esterifying HDL cholesterol (alpha-LCAT). Here we show that Tangier plasma, in contrast, has both alpha- and beta-LCAT. Thus, in both fish eye and Tangier diseases it is beta-LCAT that explains the apparent normal plasma cholesterol esterification. We also show that Tangier plasma, having alpha-LCAT activity, normalizes the low cholesteryl ester content as well as the abnormally small size of fish eye disease HDL particles during incubation.

Cholesterol↗

PubMed1987

Incidence and prevalence of juvenile chronic arthritis: a population survey.

In a population based epidemiological survey of juvenile chronic arthritis (JCA), performed in Western Sweden in 1983, an incidence of 12/100,000 was found. The estimated prevalence was 56/100,000. Subgroup distribution showed a preponderance of mono- and pauciarticular forms. The peak age of onset was between 0 and 4 years of age. Girls predominated over boys in a ratio of 3:2. Overall, 30% were antinuclear antibody (ANA) positive, 9% rheumatoid factor (RF) positive, and eye involvement occurred in 10% of the children. The results suggest differences in population based studies of JCA compared with previously reported hospital based series.

Adolescent↗

PubMed1987

Round window membrane permeability. An in vitro model.

The round window membrane is regarded to be the main route for passage of potentially ototoxic substances from the middle ear cavity into the inner ear. This is of clinical importance in acute otitis media and chronic otitis media, where sensorineural hearing impairments sometimes develop. The accuracy and reliability of an in vitro round window membrane permeability model was studied. The round window membrane of the mongolian gerbil was resected, together with its bone niche. The preparation was mounted between two glass chambers, representing the middle ear cavity and the perilymphatic space respectively. Passage through the round window membrane did not occur within 3 h for low-density lipoprotein with a molecular weight of 2,300 kD and high-density lipoprotein with a molecular weight of 115-350 kD. Horseradish peroxidase, with a molecular weight of 40 kD, passed the round window membrane at a mean rate of 6 micrograms/h when the concentration of the protein was 10 g/l in the middle ear chamber. The present in vitro model is considered to be free of leakage artifacts between the chambers. Passage rates for different substances through the round window membrane can be calculated under controlled conditions using this type of in vitro model.

Animals↗

PubMed1987

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↗

PubMed1986

Quantification of human serum apolipoprotein A-I by zone immunoelectrophoresis assay and a procedure for the preparation of an A-I standard.

A zone immunoelectrophoresis assay (ZIA) for human serum apolipoprotein A-I (Apo A-I) is described. In this immunologic technique, glass capillaries filled with agarose gel containing anti-Apo A-I are used. Apo A-I produces zones of immunoprecipitates with migration distances directly proportional to the apolipoprotein concentration. Two plasmas and their isolated high density lipoprotein (HDL) fractions, having different particle size distribution patterns have been analyzed for Apo A-I using rocket electroimmunoassay in parallel with ZIA. A good agreement between the two methods was obtained. With ZIA, Apo A-I complexed with lipids in HDL yielded concentration values that were unaffected by lipoprotein particle size and by delipidation. A standard curve, linear between 0.5 and 3.5 mg Apo A-I/1, was obtained with ZIA. A protocol for the preparation of an Apo A-I standard without prior purification of the apolipoprotein is presented. Using ZIA, 75 serum samples representing a heterogeneous study population were analyzed for Apo A-I. A mean value of 1.23 g/l with a relative standard deviation of 28% was obtained. The corresponding mean for total HDL cholesterol was 1.64 mmol/l (RSD = 61%).

Apolipoprotein A-I↗

PubMed1986

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↗

PubMed1986

Bile acid malabsorption in children and adolescents with chronic colitis.

Bile acid malabsorption was measured as the fecal excretion of 14C after intravenous administration of carboxyl-14C-cholic acid and was studied in 31 patients, 8-17 years old, with chronic colitis. There were 15 patients with proven or probable Crohn's disease and 16 patients with ulcerative colitis. The mean excretion was 14.7% and 19.9%, respectively. The patients with moderate or severe inflammatory activity in the ascending colon, assessed by colonoscopy, had a significantly higher 14C excretion than the patients with no or mild inflammatory activity, 24.1% and 6.6%, respectively. These findings suggest that the ascending colon is more important in the preservation of bile acids than has usually been postulated. When the inflammation in this part of the colon is pronounced, the 14C excretion is high, independent of the type of colitis and the clinical disease activity.

Adolescent↗

PubMed1985

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↗

PubMed1985

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↗