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Biomedical subjects

Mats Eriksson

Publications and source records attributed to Mats Eriksson.

At least 19 recordsLinked to original sources
PubMed2005

Control of ACAT2 liver expression by HNF1.

ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this report, we elucidate the mechanisms that control the liver-specific expression of the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2. Targeted deletion of the HNF1 binding site in the DNA sequence abolished not only the basal promoter function in HepG2 and HuH7 cells but also the induction of the ACAT2 promoter by HNF1. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the transcription factors HNF1alpha and HNF1beta interact with this region in the human ACAT2 gene in vitro and in vivo. These data indicate that a) the identified HNF1 binding site serves as a positive regulator sequence, b) the binding site is functionally active both in vivo and in vitro, and c) the transcription factors HNF1alpha and HNF1beta, which bind to this site, play an important part in the regulation of the human ACAT2 promoter.

Animals↗
PubMed2005

Vibrational analysis of H2 and D2 adsorption on Pt/SiO2.

Vibrational properties of surface species formed upon H2 and D2 exposure of silica supported platinum particles have been investigated with in situ diffuse reflection infrared Fourier transform spectroscopy. Experiments have been performed at 50-250 degrees C, using different platinum loading of the samples in the absence and presence of oxygen. In addition, electronic structure calculations and vibrational analysis have been performed within the density functional theory for H adsorption on a silica cluster, (HO)3SiOSi(OH)3. The spectroscopy experiments showed reversible formation of isolated OH and OD groups on the silica surface when the samples were exposed to H2 and D2, respectively. In addition to the absorption peak corresponding to isolated OH and OD groups, an intense broad band was observed around 3270 cm(-1) (2500 cm(-1)) during H2 (D2) exposure. Supported by the calculations, this band was assigned to perturbed OH groups on the silica surface. The surface coverage of new OH groups was found to correlate to the platinum loading in the samples, indicating that the new silanol groups were formed in the vicinity of the Pt particles. In the investigated temperature interval, the formation rate of OH groups was not found to be temperature dependent.

Journal Article↗
PubMed2004

ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver.

BACKGROUND: Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification. METHODS AND RESULTS: In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined. CONCLUSIONS: The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment.

Adolescent↗
PubMed2004

Levels and trends of radioactive contaminants in the Greenland environment.

Levels of radioactive contaminants in various Greenland environments have been assessed during 1999-2001. The source of 137Cs, 90Sr and (239,240)Pu in terrestrial and fresh water environments is mainly global fallout. In addition, the Chernobyl accident gave a small contribution of 137Cs. Reindeer and lamb contain the largest observed 137Cs concentrations in the terrestrial environment--up to 80 Bq kg(-1) fresh weight have been observed in reindeer. Due to special environmental conditions, 137Cs is transferred to landlocked Arctic char with extremely high efficiency in South Greenland leading to concentrations up to 100 Bq kg(-1) fresh weight. In these cases very long ecological half-lives are seen. Concentrations of 99Tc, 137Cs and 90Sr in seawater and in marine biota decrease in the order North-East Greenland and the coastal East Greenland current > South-West Greenland > Central West Greenland and North-West Greenland > Irmiger Sea-Faroe Islands. The general large-scale oceanic circulation combined with European coastal discharges and previous contamination of the Arctic Ocean causes this. As the same tendency is seen for the persistent organic pollutants (POPs) DDT and PCB in marine biota, it is suggested that long-distance oceanic transport by coastal currents is a significant pathway also for POPs in the Greenland marine environment. The peak 99Tc discharge from Sellafield 1994-1995 has only been slightly visible in the present survey year 2000. The concentrations are expected to increase in the future, especially in East Greenland. The Bylot Sound at the Thule Airbase (Pituffik) in North-West Greenland was contaminated with plutonium and enriched uranium in a weapons accident in 1968. Biological activity has mixed accident plutonium efficiently into the new sediments resulting in continued high surface sediment concentrations three decades after the accident. Transfer of plutonium to benthic biota is low--and lower than observed in the Irish Sea. This is supposed to be caused by the physico-chemical form of the accident plutonium. A recent study indicates that 'hot particles' hold considerably more plutonium than previously anticipated and that the Bylot Sound sediments may account for the major part of the un-recovered plutonium after the accident, i.e. approximately 3 kg.

Animals↗
PubMed2004

Distribution of Np and Pu in Swedish lichen samples (Cladonia stellaris) contaminated by atmospheric fallout.

The activity concentrations of (237)Np and the two Pu isotopes, (239)Pu and (240)Pu, were determined in lichen samples (Cladonia stellaris) contaminated by fallout from atmospheric nuclear test explosions and the Chernobyl accident. The samples were collected at 18 locations in Sweden, from north to south, between 1986 and 1988 and analysed with high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) and alpha spectrometry. Data on the activity ratios (238)Pu/(239+240)Pu and (134)Cs/(137)Cs measured previously were also included in this study for comparison. The (237)Np activity concentration ranged from 0.08 +/- 0.01 to 2.08 +/- 0.17 MBq kg(-1), depending on the location of the sampling site and time of collection. The (239+240)Pu activity concentration ranged from 0.09 +/- 0.01 to 4.09 +/- 0.15 Bq kg(-1), with the (240)Pu/(239)Pu atomic ratio ranging between 0.16 +/- 0.01 and 0.44 +/- 0.03, the higher ratios indicating a combination of weapons test fallout and Chernobyl fallout. The (237)Np/(239)Pu atomic ratios ranged between 0.06 +/- 0.01 and 0.42 +/- 0.04, the lower ratios indicating combination of weapons test fallout and Chernobyl fallout. At a well-defined sampling site at Lake Rogen (62.32 degrees N, 12.38 degrees E), additional lichen samples were collected between 1987 and 1998 to study the distribution of Np and Pu in different layers. The concentrations of the two elements follow each other quite well in the profile.

Air Pollutants, Radioactive↗
PubMed2004

Can daily repeated doses of orally administered glucose induce tolerance when given for neonatal pain relief?

AIM: Orally administered sweet solutions have a pain-relieving effect during painful procedures in newborn infants. The underlying mechanism is not fully understood, but, from the results of animal research, an opioid-like mechanism is often suggested. The aim of this study was to determine whether repeated doses of orally administered glucose would cause tolerance to glucose. METHODS: Fifty-seven healthy, full-term infants were recruited on the day of birth to receive three daily doses of either 1 ml 30% glucose or sterile water for 3-5 d, after which routine blood samples were collected by heel-lance. All infants received 1 ml 30% glucose before the heel-lance was carried out. Crying time, Premature Infant Pain Profile scores and changes in heart rate were used as pain measures. RESULTS: No differences were found between the groups, either in demographic data or in the outcome variables. CONCLUSION: No tolerance was observed under the conditions prevailing in this study. However, we cannot rule out an endogenous opioid mechanism. What is clinically important is that repeated doses of glucose do not decrease the pain-relieving effect.

Amino Acids↗
PubMed2004

Genetic dissection of nutritional copper signaling in chlamydomonas distinguishes regulatory and target genes.

A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2 (CRD2), distinguished as regulatory or target genes on the basis of phenotype. CRR1 was shown previously to be required for transcriptional activation of target genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c(6) (which is a heme-containing substitute for copper-containing plastocyanin), coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase. We show here that CRR1 is required also for normal accumulation of copper proteins like plastocyanin and ferroxidase in copper-replete medium and for apoplastocyanin degradation in copper-deficient medium, indicating that a single pathway controls nutritional copper homeostasis at multiple levels. CRR1 is linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a gain-of-function mutation resulting in copper-independent expression of CYC6. CRR1 is required also for hypoxic growth, pointing to a physiologically meaningful regulatory connection between copper deficiency and hypoxia. The growth phenotype of crr1 strains results primarily from secondary iron deficiency owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper distribution to a multicopper ferroxidase involved in iron assimilation. Mutations at the CRD2 locus also result in copper-conditional iron deficiency, which is consistent with a function for CRD2 in a pathway for copper delivery to the ferroxidase. Taken together, the observations argue for a specialized copper-deficiency adaptation for iron uptake in Chlamydomonas.

Animals↗
PubMed2003

Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock.

INTRODUCTION: Antibiotics used for treatment of severe bacterial infections have been shown to exert effects on the inflammatory response in addition to their antibacterial effects. The aim of the present study was to investigate whether the biological effects of endotoxin in a porcine model could be neutralized by tobramycin, and whether tobramycin or ceftazidime was able to modulate the inflammatory response. METHOD: Thirteen piglets were subjected to endotoxin infusion at an initial rate of 4 microgram/kg per hour, which was reduced to 1 microgram/kg per hour after 30 min. Before endotoxin infusion, the animals received saline (n = 4), ceftazidime (n = 5), or tobramycin (n = 4) at clinically relevant doses. Physiological parameters were measured and blood samples were taken hourly for 6 hours for analysis of tumour necrosis factor-alpha, IL-6 and endotoxin concentrations. RESULTS: All of the animals exhibited physiological signs of severe sepsis without major differences between the groups. Plasma endotoxin concentration was stable after 1 hour. There were no differences in endotoxin concentration or initial tumour necrosis factor-alpha and IL-6 concentrations between the groups. At 6 hours the IL-6 concentration was significantly lower in the ceftazidime group than in the saline group (P < 0.05), and in both the ceftazidime and the tobramycin groups there were significantly greater reductions from peak values (P < 0.05). CONCLUSION: There was no neutralization of the biological effects of endotoxin in this porcine model. However, our data indicate a possible anti-inflammatory effect exerted by both ceftazidime and tobramycin, which manifested as a significantly greater reduction in IL-6 in comparison with the untreated group.

Animals↗
PubMed2003

Growth hormone induces low-density lipoprotein clearance but not bile acid synthesis in humans.

OBJECTIVE: Growth hormone (GH) induces hepatic low-density lipoprotein (LDL) receptors and lowers plasma cholesterol. We characterized the influence of GH treatment on plasma LDL clearance in normal humans and investigated the relative role of LDL receptor (LDLR) activity and stimulation of bile acid synthesis in subjects with different LDLR expression. METHODS AND RESULTS: Plasma clearance of autologous 125I-LDL was measured before and during 3 weeks of treatment with GH (0.1 IU/kg per day) in 9 healthy young males. Plasma LDL cholesterol was reduced by 13% and the fractional catabolic rate of LDL increased by 27%. More marked changes were seen in a patient with hypopituitarism substituted with GH (0.07 IU/kg per day) for 3 months. In a second study, GH dose-dependently reduced LDL cholesterol and increased Lp(a) levels in 3 groups of males: younger and elderly healthy subjects and heterozygous familial hypercholesterolemia (FH). No effect on bile acid synthesis measured by the plasma marker 7alpha-hydroxy-4-cholesten-3-one was observed. In an LDLR-deficient FH homozygote, LDL cholesterol was not affected by GH. CONCLUSIONS: GH treatment reduces plasma LDL cholesterol by inducing LDL clearance. In humans, LDLR expression is a prerequisite for this effect, whereas it is not related to stimulation of bile acid synthesis.

Adult↗
PubMed2003

A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study.

BACKGROUND: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. OBJECTIVE: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (<or=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. RESULTS: The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation fo the drugs' effects on TG. Patient demogrpahic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%; P < 0.001). Fewer atorvastatin patients needed to have their dose doubled; nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group. CONCLUSIONS: Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d in reducing LDL-C and TG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statis were well tolerated.

Adult↗
PubMed2003

CSF taurine level is influenced by plasma cholesterol and the CYP2D6 phenotype.

Eight healthy male volunteers, lumbar-punctured before and during simvastatin treatment, were phenotyped for CYP2D6 analysis of the debrisoquine metabolic ratio (the ratio between the urinary recovery of debrisoquine and its 4-hydroxy metabolite) after a single oral dose of debrisoquine. The mean cerebrospinal fluid concentrations of cholesterol and taurine did not differ before and during treatment. During (but not before) treatment taurine in the CSF correlated with the debrisoquine metabolic ratio (r=-0.93; P=0.0007) Our results might indicate an influence of CYP2D6 on the level of taurine in the CSF that was secondary to the change in plasma cholesterol.

Adult↗
PubMed2003

Micro- and macrocirculatory effects of apheresis in patients with familial hyperlipidemia.

High lipid levels have been shown to coexist with a disturbed vascular endothelial function. Thus, acute lipid lowering could be expected to improve vascular reactivity. Patients with familial hyperlipidemia (FH) have substantial and rapid decreases in lipid levels after low-density lipoprotein apheresis. Thus, an opportunity exists to study acute effects of lipid lowering on vascular reactivity. Flow mediated vasodilation (FMD) is commonly used to assess endothelial function in conduit vessels, whereas vital capillary microscopy during the post-reactive hyperemia (PRH) phase is used to assess response at the microvascular level. It is not known whether endothelial dysfunction is a general phenomenon in all kinds of vessels or if there are differences between micro- and macrovessels. In the present study, we were not able to demonstrate an improved vascular response after acute lipid lowering in FH patients. This was true both in the microcirculation (PRH) and in the conduit vessels (FMD). However, the two methods gave concordant results, demonstrating disturbed vascular reactivity in the patients as compared with healthy subjects. We have found no previous report with parallel assessments at the microcirculatory and macrocirculatory levels.

Adult↗
PubMed2003

Influence of nervous blockade on insulin-mediated glucose uptake in the human forearm.

This study was undertaken to investigate if a nonpharmacologic increase in forearm blood flow (FBF) could increase forearm glucose uptake (FGU) during hyperinsulinemia. In 10 young volunteers, FBF and the arterial-venous glucose difference were measured in both arms during a 2-hour euglycemic hyperinsulinemic clamp procedure when 1 of the arms was subjected to axillary plexus nervous blockade with local anesthesia. FBF was measured in both arms by venous occlusion plethysmography. Nervous blockade, increasing FBF by more than 3-fold, did not improve insulin-mediated FGU. On the contrary, a tendency towards a reduced FGU compared with the control arm was seen (P =.07). Furthermore, while insulin increased FBF to a similar degree in both arms (+ 3.0 and 4.4 mL/min/100 mL tissue, P <.01 for both arms), nervous blockade abolished the rapid increase in glucose extraction seen in the control arm when insulin infusion was initiated. The present study showed that an increase in FBF induced by nervous blockade did not increase insulin-mediated FGU. On the contrary, a tendency towards a reduction was seen. Furthermore, insulin induced vasodilation in the blocked arm, but delayed the ability of insulin to promote glucose extraction, suggesting that the well-documented increase in skeletal muscle sympathetic nerve activity seen during acute hyperinsulinemia has metabolic rather than hemodynamic consequences.

Adult↗
PubMed2003

An anaplerotic role for mitochondrial carbonic anhydrase in Chlamydomonas reinhardtii.

Previous studies of the mitochondrial carbonic anhydrase (mtCA) of Chlamydomonas reinhardtii showed that expression of the two genes encoding this enzyme activity required photosynthetically active radiation and a low CO(2) concentration. These studies suggested that the mtCA was involved in the inorganic carbon-concentrating mechanism. We have now shown that the expression of the mtCA at low CO(2) concentrations decreases when the external NH(4)(+) concentration decreases, to the point of being undetectable when NH(4)(+) supply restricts the rate of photoautotrophic growth. The expression of mtCA can also be induced at supra-atmospheric partial pressure of CO(2) by increasing the NH(4)(+) concentration in the growth medium. Conditions that favor mtCA expression usually also stimulate anaplerosis. We therefore propose that the mtCA is involved in supplying HCO(3)(-) for anaplerotic assimilation catalyzed by phosphoenolpyruvate carboxylase, which provides C skeletons for N assimilation under some circumstances.

Animals↗
PubMed2002

Reverse cholesterol transport in man: promotion of fecal steroid excretion by infusion of reconstituted HDL.

Reverse cholesterol transport is a complex process, which transfers cholesterol from peripheral cells to the liver for subsequent elimination as bile acids and neutral steroids. Although apo A-I in high density lipoproteins (HDL) is believed to have a crucial role in this process, clinical conditions with very low HDL cholesterol levels appear to maintain normal cholesterol excretion. On the other hand, infusion of 'artificial HDL' in the form of recombinant proapo A-I (4 g) liposome complexes results in increased fecal steroid excretion, corresponding to a removal of approximately 0.5 g cholesterol daily for up to 9 days. This occurs without evidence of increased cholesterol synthesis, and could not be reproduced by infusion of liposomes only. These data indicate that stimulation of reverse cholesterol transport may be induced by infusion of 'artificial HDL' in humans, and that a more detailed knowledge of this process may be useful in the treatment of atherosclerosis.

Arteriosclerosis↗
PubMed2002

Effects of blockade of alpha- and beta-adrenoceptors and neuropeptide Y(1) receptors, as well as brachial plexus blockade, on endothelium-dependent vasodilation in the human forearm.

1. The aim of the present study was to investigate the effects of alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol), neuropeptide Y(1) receptor blockade and neurogenic blockade (brachial plexus) on endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation (EIDV)). These measurements were undertaken at baseline and were repeated with either concomitant local intra-arterial infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the forearm, neuropeptide Y(1) receptor blockade (n = 12) given i.v. or during axillary plexus blockade (n = 11). 3. Both alpha-adrenoceptor blockade and neurogenic blockade induced an upward shift in the dose-response curve for both EDV and EIDV. beta-Adrenoceptor blockade did not change resting FBF or EIDV, but induced a significant decrease in EDV (P = 0.015). Neuropeptide Y(1) receptor blocker induced no significant changes in resting FBF, EDV and EIDV and neither did saline. No changes in blood pressure or heart rate were induced by any of the blockades. 4. Whereas beta-adrenoceptor blockade impaired EDV, alpha-adrenoceptor blockade and neurogenic blockade caused a general vasodilation that was not endothelium dependent. Neuropeptide Y does not seem to influence blood flow in the resting forearm.

Adrenergic alpha-Antagonists↗