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Biomedical subjects

M Eriksson

Publications and source records attributed to M Eriksson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans.

BACKGROUND: Apolipoprotein (apo) A-I is the major protein component of HDL, a cholesterol transport particle that protects against atherosclerosis. Apo A-I is believed to promote reverse cholesterol transport, transferring cholesterol from peripheral cells to the liver for subsequent elimination. To test this hypothesis in humans, we measured fecal steroid excretion before and after the intravenous infusion of human proapo A-I (precursor of apo A-I) liposome complexes. METHODS AND RESULTS: Four subjects with heterozygous familial hypercholesterolemia w re studied under standardized conditions. The fecal excretion of bile acids and neutral sterols was determined for 9 days before and 9 days after an intravenous infusion of recombinant human proapo A-I (4 g protein) liposome complexes. Plasma apoA-I and HDL cholesterol levels increased transiently (mean peak concentrations were 64% and 35% above baseline, respectively) during the first 24 hours. Mean lipoprotein lipid and apolipoprotein levels were not different during the 2 collecting periods, however. Serum lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, was also unchanged. The fecal excretion of cholesterol (neutral sterols and bile acids) increased in all subjects (mean increase, +39% and +30%, respectively), corresponding to the removal of approximately 500 mg/d excess cholesterol after infusion. Control infusions with only liposomes in 2 of the patients did not influence lipoprotein pattern or cholesterol excretion. CONCLUSIONS: Infusion of proapoA-I liposomes in humans promotes net cholesterol excretion from the body, implying a stimulation of reverse cholesterol transport. This mechanism may prove useful in the treatment of atherosclerosis.

Adult↗
PubMed1999

Evidence for 4-hydroxyproline in viral proteins. Characterization of a viral prolyl 4-hydroxylase and its peptide substrates.

4-Hydroxyproline, the characteristic amino acid of collagens and collagen-like proteins in animals, is also found in certain proline-rich proteins in plants but has been believed to be absent from viral and bacterial proteins. We report here on the cloning and characterization from a eukaryotic algal virus, Paramecium bursaria Chlorella virus-1, of a 242-residue polypeptide, which shows distinct sequence similarity to the C-terminal half of the catalytic alpha subunits of animal prolyl 4-hydroxylases. The recombinant polypeptide, expressed in Escherichia coli, was found to be a soluble monomer and to hydroxylate both (Pro-Pro-Gly)(10) and poly(L-proline), the standard substrates of animal and plant prolyl 4-hydroxylases, respectively. Synthetic peptides such as (Pro-Ala-Pro-Lys)(n), (Ser-Pro-Lys-Pro-Pro)(5), and (Pro-Glu-Pro-Pro-Ala)(5) corresponding to proline-rich repeats coded by the viral genome also served as substrates. (Pro-Ala-Pro-Lys)(10) was a particularly good substrate, with a K(m) of 20 microM. The prolines in both positions in this repeat were hydroxylated, those preceding the alanines being hydroxylated more efficiently. The data strongly suggest that P. bursaria Chlorella virus-1 expresses proteins in which many prolines become hydroxylated to 4-hydroxyproline by a novel viral prolyl 4-hydroxylase.

Amino Acid Sequence↗
PubMed1999

A case-control study of non-Hodgkin lymphoma and exposure to pesticides.

BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased in most Western countries during the last few decades. Immunodefective conditions are established risk factors. In 1981, the authors reported an increased risk for NHL following exposure to certain pesticides. The current study was designed to further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL. METHODS: A population-based case-control study in northern and middle Sweden encompassing 442 cases and twice as many controls was performed. Exposure data were ascertained by comprehensive questionnaires, and the questionnaires were supplemented by telephone interviews. In total, 404 cases and 741 controls answered the questionnaire. Univariate and multivariate analyses were performed with the SAS statistical data program. RESULTS: Increased risk for NHL was found for subjects exposed to herbicides (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.5) and fungicides (OR, 3.7; 95% CI, 1.1-13.0). Among herbicides, the phenoxyacetic acids dominated (OR, 1.5; 95% CI, 0.9-2.4); and, when subclassified, one of these, 4-chloro-2-methyl phenoxyacetic acid (MCPA), turned out to be significantly associated with NHL (OR, 2.7; 95% CI, 1.0-6.9). For several categories of herbicides, it was noted that only exposure during the most recent decades before diagnosis of NHL was associated with an increased risk of NHL. Exposure to impregnating agents and insecticides was, at most, only weakly related to NHL. CONCLUSIONS: Exposure to herbicides in total, including phenoxyacetic acids, during the decades before NHL diagnosis resulted in increased risk for NHL. Thus, the risk following exposure was related to the latency period. Fungicides also increased the risk for NHL when combined, but this group consisted of several different agents, and few subjects were exposed to each type of fungicide.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1999

Aerobic degradation of a hydrocarbon mixture in natural uncontaminated potting soil by indigenous microorganisms at 20 degrees C and 6 degrees C.

A hydrocarbon mixture containing p-xylene, naphthalene, Br-naphthalene and straight aliphatic hydrocarbons (C14 to C17) was aerobically degraded without lag phase by a natural uncontaminated potting soil at 20 degrees C and 6 degrees C. Starting concentrations were approximately 46 ppm for the aromatic and 13 ppm for the aliphatic compounds. All aliphatic hydrocarbons were degraded within 5 days at 20 degrees C, to levels below detection (ppb levels) but only down to 10% of initial concentration at 6 degrees C. Naphthalene was degraded within 12 days at 20 degrees C and unaffected at 6 degrees C. At 20 degrees C p-xylene was degraded within 20 days, but no degradation occurred at 6 degrees C. Br-naphthalene was only removed down to 30% of initial concentration at 20 degrees C, with no significant effect at 6 degrees C. The biodegradation was monitored with head space solid-phase microextraction and gas chromatography-mass spectrometry.

Aerobiosis↗
PubMed1999

Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects lumbar-punctured without preceding strict bed-rest.

In a recent study we analysed the concentrations of two forms of cholecystokinin (CCK), CCK-8S (sulphated) and CCK-4 in cerebrospinal fluid (CSF) obtained from 14 healthy male volunteers lumbar-punctured after a minimum of eight hours of strict bed-rest. We have now lumbar-punctured another group of 14 healthy males, using the same procedure except for the requirement of strict bed-rest prior to puncture. In contrast to our previous study, the concentration of CCK-4 (but not CCK-8S) was significantly higher in the second CSF fraction (7-12 ml) than in the first one (0-6 ml). On using the concentration ratio between the second and first fraction, CCK-8S (but not CCK-4) correlated positively with the atmospheric pressure, which is in contrast to our previous study in which a significant negative correlation was found. When the lumbar CSF concentrations were expressed as the concentration per minute of tapping-time (an estimate of the mass flow), atmospheric pressure, age and the neuraxis distance in the lying position made significant contributions to the variance in CCK-8S. A significant positive correlation with atmospheric pressure was found for CCK-4. In conclusion, the results indicate that the question of strict bed-rest or not prior to lumbar puncture may have to be considered when interpreting data on lumbar CSF concentrations of CCK. A controlled study is warranted.

Adult↗
PubMed1999

Neutrophil dysplasia is not a specific feature of the abnormal chromosomal clone in myelodysplastic syndromes.

In order to study if dysplastic cells are part of the abnormal chromosomal clone in myelodysplastic syndromes (MDS) we used fluorescence in situ hybridization in combination with standard May-Grünwald-Giemsa morphology (MGG/FISH) to investigate the penetration of chromosomal abnormalities into dysplastic neutrophil granulocytes in five MDS patients with documented monosomy 7 or trisomy 8 in the bone marrow at diagnosis. Neutrophil dysplasia was defined as neutrophil granulocytes with extreme hypogranulation or with nuclear abnormalities of the pelgeroid type. In one patient all dysplastic cells were derived from the abnormal chromosomal clone, while in the other four cases only 6-43% of the hypogranulated neutrophils and 33-40% of the pelgeroid granulocytes exhibited the chromosomal marker. The results suggest that neutrophil dysplasia is not a specific feature of the abnormal chromosomal clone in MDS. It is not clear, however, if the disomic dysplastic cells were derived from a parallel MDS clone with a normal karyotype, or represent residual non-clonal, normal hematopoietic cells.

Aged↗
PubMed1999

Oral glucose and venepuncture reduce blood sampling pain in newborns.

The objectives of this study were to measure pain symptoms in healthy fullterm newborns undergoing routine blood sampling with different methods. The 120 study subjects were randomly allocated to one of four groups with 30 babies in each, namely venepuncture or heel stick, with or without oral glucose administration. Pain was assessed from the duration of crying within the first 3 min, the Premature Infant Pain Profile (PIPP) and changes in heart rate. When the babies received 1 ml 30% glucose prior to skin puncture there was no significant difference between the heel stick and venepuncture group either in mean crying time (12.9 and 11.6 s, respectively) or in PIPP score (3.9 and 3.3). When no glucose was given crying time was 57.3 s in the heel stick group and 26.8 s in the venepuncture group (P = 0.0041) and the mean PIPP scores were 8.4 and 6.0, respectively (P = 0.0458). This study suggests that if oral glucose is given prior to skin puncture the choice of blood sampling method has no impact on the pain symptoms.

Administration, Oral↗
PubMed1999

The influence of frusemide formulation on diuretic effect and efficiency.

AIMS: Changes in drug delivery rate may result in clinically important changes in drug effects. For the loop diuretic frusemide, it would be desirable to develop controlled release preparations, that could maintain an effective urinary excretion rate over a prolonged period of time. The aim of this study was to investigate the influence of frusemide formulation on frusemide recovery, diuretic effect and efficiency. METHODS: Twelve subjects were given 60 mg of four different frusemide controlled release formulations in a single-dose, double-blind, randomized 4-way cross-over design. The formulations were three study drugs with different extended dissolution rates (ER1Tab, ER2Tab and ER3Caps ) and one reference drug (LR). Urinary volume and contents of frusemide in urine were measured in samples collected over 24 h. RESULTS: Substantial differences in frusemide recovery and diuretic efficiency were observed between LR and all other formulations. At 24 h, mean total frusemide recoveries of ER1Tab, ER2Tab and ER3Caps were 52%, 36% and 57% lower, respectively, compared with LR (P<0.01). Also at 24 h, mean total diuretic efficiency for ER1Tab, ER2Tab and ER3Caps was 83%, 31% and 135% higher, respectively, compared to LR. The rapid dissolution and absorption of LR resulted in a high diuretic response from 0 to 3 h after dosing. However, from 0 to 24 h, there were no differences in diuretic response between the formulations. CONCLUSIONS: Controlled release formulations of frusemide with a low and extended rate of dissolution lead to a more prolonged absorption and subsequent diuresis, but still maintain a similar cumulative response, due to their higher diuretic efficiency.

Adolescent↗
PubMed1999

Acidified propofol retains its anaesthetic potency after storage.

The reduction in propofol-induced pain on injection caused by the addition of lignocaine results mainly from a drop in pH, which reduces the concentration of propofol in the aqueous phase of the emulsion. It is not an effect of the local anaesthetic per se. Propofol emulsion mixed with lignocaine destabilizes within hours. We mixed 10 parts of propofol 1% emulsion with one part of 0.0064 M HCl or 0.013 M HCl, respectively. These mixtures were stored for 3 months and compared with a freshly prepared solution of propofol 1% emulsion and saline, in the same proportion, regarding their ability to induce anaesthesia in the rat. There was no significant difference in the amount of propofol required to induce anaesthesia, nor was there any difference in recovery time between the three groups.

Anesthetics, Intravenous↗
PubMed1999

The anaesthetic potency of propofol in the rat is reduced by simultaneous intravenous administration of lignocaine.

Lignocaine added to the anaesthetic preparation Diprivan reduces propofol induced pain on injection. This effect is due to a drop in pH which decreases the content of propofol in the aqueous phase of the soya bean emulsion. This in turn changes the electrostatic forces in the emulsion and destabilization occurs. The effect of lignocaine on the anaesthetic potency of propofol was validated in a randomized blind study in the rat. The induction dose of 1% propofol mixed with 1% lignocaine (10 + 1) was significantly higher when compared with the induction dose of propofol 1% given after a separate injection of 1% lignocaine (9.4 +/- 5.5 vs. 5.6 +/- 5.2 mg; P < 0.05). The duration of sleep was shorter in rats injected with propofol 1% mixed with lignocaine 1% (10 + 1) compared with those given 1% lignocaine and 1% propofol in separate injections (160 +/- 181 vs. 375 +/- 202 s; P < 0.05). The anaesthetic potency of propofol was not significantly changed by the addition of either saline or hydrochloric acid. The anaesthesia inducing effect was not time-dependent. A similar lower potency was observed for a solution stored for 4 h compared with one freshly prepared, although sleeping time was longer (9.2 +/- 6.8 mg; 428 +/- 110 s) as compared with the 4 h mixture. The results indicate that lignocaine altered the propofol preparation. The reduced anaesthetic potency of propofol after addition of lignocaine is not due to the resultant drop in pH, which is known to occur.

Anesthesia, Intravenous↗
PubMed1999

Evidence of circadian rhythm in low-density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters.

BACKGROUND: Compartmental models with constant parameters are commonly used in kinetic analysis of low-density lipoproteins (LDLs). Recent studies in animals have demonstrated the existence of circadian rhythms (CRs) in cholesterol synthesis and LDL catabolism. In this study, we investigated the possible existence of a CR in the fractional catabolic rate (FCR) of LDL apoB in man. MATERIALS AND METHODS: Radioactivity data from 45 turnover studies using 125I-labelled LDL apoB were analysed. In a preliminary analysis the pattern of radioactivity decay was investigated. Kinetic analysis was performed by using one- and two-compartment models with constant parameters (steady-state, SS, analysis). Parameters were estimated by the use of the whole data set, which included frequent sampling during the first day of the turnover study, or the once-a-day data, taken at 08.00 h. The selection of once-a-day data allowed elimination of the impact of a CR on parameter evaluation. Furthermore, non-steady-state (NSS) analysis was performed in which the FCR of LDL apoB was calculated as a function of time. In one additional subject, the FCR of LDL apoB was calculated separately for the day and the night using the urine-to-plasma (U/P) radioactivity ratio. RESULTS: The presence of a CR in LDL apoB catabolism, with higher FCR values during the day than during the morning, was demonstrated by the NSS analysis and confirmed by LDL apoB calculation from the U/P ratio. The SS analysis with the whole and the once-a-day data sets resulted in similar average FCR of apoB values (0.329 +/- 0.076 and 0.321 +/- 0.071 respectively) when the two-compartment model was used. Thus, a CR appeared to have little impact on the average FCR of apoB estimation. However, frequent sampling used in the hope of improving parameter estimation accuracy actually resulted in deterioration of the intercompartmental parameter estimators. CONCLUSION: The fractional catabolic rate of LDL apoB exhibited a circadian rhythm with higher FCR values during the day than during the morning. The presence of a CR had, however, a limited impact on the overall FCR of apoB values.

Apolipoproteins B↗
PubMed1999

Ly49A inhibitory receptors redistribute on natural killer cells during target cell interaction.

When T effector cells meet antigen-bearing target cells, there is a specific accumulation of T-cell receptors, co-receptors and structural proteins at the point of cell-cell contact. Ly49 inhibitory receptors bind to murine major histocompatibility complex (MHC) class I molecules and prevent natural killer-(NK) cell cytotoxicity. In this study we have tested whether inhibitory receptors accumulate at the point of cell-cell contact when NK cells encounter target cells bearing MHC class I ligands for those inhibitory receptors. We have used RNK-16 effector cells that express Ly49A receptors and have found that there was a specific accumulation of Ly49A receptors at the point of NK cell-target cell contact when the target cells expressed H-2Dd. We also observed that engagement of Ly49A on NK cells resulted in an altered redistribution of potential triggering receptors CD2 and NKR-P1. These data indicate that inhibitory receptors, like activating receptors, may specifically aggregate at the point of cell-cell contact which may be necessary for them to mediate their full inhibitory effect.

Animals↗
PubMed1999

H-2Dd engagement of Ly49A leads directly to Ly49A phosphorylation and recruitment of SHP1.

We have used a number of in vitro and in vivo techniques to identify the molecules that can bind to the cytoplasmic tail of the Ly49A receptor. Affinity chromatography using peptides corresponding to the N-terminal 18 amino acids of Ly49A allowed the recovery of a number of proteins that bound preferentially to the tyrosine-phosphorylated peptide, including SH2-containing phosphatase-1 (SHP1) and the SH2-containing inositol 5' phosphatase (SHIP). In another approach, using the entire cytoplasmic domain of the Ly49A receptor, we found that SHP2 also interacted with the tyrosine-phosphorylated form of the Ly49A cytoplasmic tail. Using BIACORE(R)2000 analysis, we determined that both SHP1 and SHP2 bound to the tyrosine-phosphorylated cytoplasmic tail of Ly49A with affinities in the nanomolar range, whilst SHIP showed no binding. Mutation of tyrosine-36 to phenylalanine did not significantly affect the affinities of these proteins for the tyrosine-phosphorylated cytoplasmic tail of Ly49A. In addition, using a whole-cell system with T-cell lymphoma cell lines that expressed the Ly49A receptor or its H-2Dd ligand, we determined that engagement of Ly49A by its major histocompatibility complex (MHC) ligand leads to tyrosine-phosphorylation events and recruitment of SHP1. Recruitment of SHP1 was rapid and transient, reaching a maximum after 5 min. These data suggest that mechanisms for the inhibitory signal are generated following receptor engagement. They also provide direct evidence that ligand engagement of the Ly49A receptor is responsible for recruitment of downstream signalling molecules.

Animals↗
PubMed1999

DNA binding of lambda- and delta-cis-beta-[Ru(RR-picchxn)(phen)](2)+ studied by NMR and flow linear dichroism spectroscopy.

Two novel substitutionally-inert diastereomeric ruthenium(II) cations of the form lambda- and delta-cis-beta-[Ru(RR-picchxn)(phen)]2+, where RR-picchxn is N,N'-dimethyl-N,N'-di(2-picolyl)-1R,2R-diaminocyclohexane and phen is 1,10-phenanthroline, have been studied with respect to their interactions with duplex DNA. NMR investigations show that both diastereomers bind to the oligonucleotide [d(CGCGATCGCG)]2 in the fast exchange regime and that binding predominantly takes place in the minor groove of the oligonucleotide, but that the governing interactions are significantly different for the two delta and lambda forms. Linear dichroism data support the latter interpretation, in that the relative orientations of cis-beta-[Ru(RR-picchxn)(phen)]2+ to calf thymus DNA also are observed to differ for the delta and lambda diastereomers. Interpretation of these data indicates the lambda form to be bound with the planar phen ligand closely parallel to the DNA base-pairs, but the average orientation of the phen ligand in the delta form deviates significantly from a parallel alignment.

Animals↗
PubMed1999

Contribution of interleukin-6 in distinguishing between mild respiratory disease and neonatal sepsis in the newborn infant.

The purpose of this study was to investigate if early samples of interleukin-6 (IL-6) could distinguish early bacterial sepsis from respiratory diseases in the newborn. IL-6 and C-reactive protein (CRP) were measured at onset of symptoms in newborns evaluated for sepsis during the first week of life. Five groups of children were investigated: proven sepsis, clinical sepsis, respiratory distress syndrome (RDS), transient tachypnoea of the newborn (TTN) and controls. IL-6 was also analysed at the time when CRP was at its maximum level. The results showed that initial IL-6 distinguished proven and clinical sepsis from TTN, but not from RDS. Initial CRP was of no value for diagnosis. Our conclusion is that early IL-6 makes it possible to avoid antibiotics in children with TTN and contributes to the diagnosis of sepsis faster than CRP.

Bacterial Infections↗
PubMed1999

The extended Biocor stentless aortic bioprosthesis. Early clinical experience.

In the "Extended" Biocor stentless aortic bioprosthesis, supra- and subvalvular extensions to a bovine pericardium ring carry three porcine leaflets. The extensions cover the "non-coronary" sinus of the prosthesis and allow optional enlargement of the aortic root down towards the mitral valve as well as upwards into the aortotomy. Seventy-one patients with this stentless valve (62 with predominantly aortic stenosis, 28 with concomitant CABG) are being prospectively studied. This paper reports follow-up one year after insertion. The upper and lower pericardial extensions were used in 61 and 11 patients, respectively. The average prosthetic valve size was 23.2 +/- 1.6 mm. Early mortality was 7% (5/71); late mortality (4/66, 5%/patient year) was not valve-related. Symptoms of thromboembolism (new neurological defects) occurred in four patients. There was no valve failure or late endocarditis. One year postoperatively the transvalvular mean pressure difference for all valves was 7.9 (3.1-18.4) mmHg. None of the patients had haemodynamically significant aortic regurgitation at follow-up; nine had trivial regurgitation. The "Extended" Biocor stentless bioprosthesis thus has a favourable haemodynamic profile and can be advantageous in elderly patients with narrow aortic roots, and often with thin and/or calcified aortic walls.

Aged↗
PubMed1999

Simultaneous analysis of expression of the three myotonic dystrophy locus genes in adult skeletal muscle samples: the CTG expansion correlates inversely with DMPK and 59 expression levels, but not DMAHP levels.

The causative mutation in the majority of cases of myotonic dystrophy has been shown to be the expansion of a CTG trinucleotide repeat, but the mechanism(s) by which this repeat leads to the very complex symptomatology in this disorder remains controversial. We have developed a highly sensitive and quantifiable assay, based on competitive RT-PCR, to test the hypothesis that the expansion disrupts the expression of the genes in its immediate vicinity, DMPK, 59 and DMAHP. In order to avoid cell culture-induced artifacts we performed these experiments using adult skeletal muscle biopsy samples and analysed total cytoplasmic poly(A)+mRNA levels for each gene simultaneously, as this is more physiologically relevant than allele-specific levels. There was considerable overlap between the expression levels of the three genes in myotonic dystrophy patient samples and samples from control individuals. However, in the myotonic dystrophy samples we detected a strong inverse correlation between the repeat size and the levels of expression of DMPK and 59. This is the first report of a possible effect of the CTG expansion on gene 59. Our results indicate that whilst a simple dosage model of gene expression in the presence of the mutation is unlikely to be sufficient in itself to explain the complex molecular pathology in this disease, the repeat expansion may be a significant modifier of the expression of these two genes.

Adult↗