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Biomedical subjects

M Eriksson

Publications and source records attributed to M Eriksson.

At least 325 records · Page 18Linked to original sources

Solution structure of human plasma fibronectin as a function of NaCl concentration determined by small-angle X-ray scattering.

The structure of human plasma fibronectin in 50 mM Tris-HCl buffer, pH 7.4, containing varying concentrations of NaCl, has been investigated using the small-angle X-ray method. Below 0.3 M NaCl the overall structure of the molecule is disc-shaped; at 0 M NaCl the axial ratio of the disc is about 1:7 and between 0.1 M to 0.3 M it is slightly more asymmetric, with an axial ratio of 1:10. At about 0.3 M NaCl there is a reversible transition to a more open structure, and, from 0.3 M up to 1.1 M NaCl the small-angle X-ray data can be explained by models consisting of ensembles of flexible, non-overlapping, bead-chains generated by a Monte Carlo procedure. Within this concentration range there is a gradual increase in the stiffness of the chains, as well as a decrease in bead radius, which indicates that the molecule becomes more open when the NaCl concentration is increased. The transition to a more open structure is also demonstrated by the average radius of gyration which increases gradually from 8.26 nm at 0 M NaCl to 8.75 nm at physiological or near-physiological conditions, and up to 16.2 nm at 1.1 M NaCl.

Fibronectins↗

Interaction of ellipticine and an indolo[2,3b]-quinoxaline derivative with DNA and synthetic polynucleotides.

The non-covalent DNA interaction of the anticancer drug ellipticine (Scheme I, 1a) as well as an indolo[2,3-b]-quinoxaline derivative (Scheme I, 3b) with a dimethylaminoethyl side chain has been studied by light absorption, linear dichroism (LD) and fluorescence. Compound 3b (Scheme I) has antitumorigenic as well as antiviral activity. Both compounds bind to DNA or synthetic polynucleotides such as poly(dA-dT).(dA-dT) and poly(dG-dC).(dG-dC) by intercalation. In contrast to ellipticine, compound 3b (Scheme I) exhibits a significant binding specificity for alternating AT sequences. Its fluorescence is strongly enhanced in AT sequences and quenched in GC sequences. Fluorescence titrations evaluated as Scatchard plots show that both ellipticine and compound 3b (Scheme I) bind to the nucleic acids according to a non-cooperative neighbor exclusion model.

Alkaloids↗

Oestrogen-induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit.

Administration of moderate pharmacological doses of oestrogen to cholesterol-fed rabbits for 12 weeks resulted in a dramatically retarded development of arterial lesions as compared to non-oestrogen-treated, cholesterol-fed rabbits (7% vs. 47% aortal involvement). Oestrogen treatment was associated with a retarded increase in plasma cholesterol, and five times higher high density lipoprotein (HDL) to very low density lipoprotein (VLDL) cholesterol ratio. Expression of hepatic lipoprotein receptor activity, as detected by heparin-releasable binding of 125I-hypercholesterolaemic VLDL, was heavily suppressed by cholesterol feeding. Administration of oestrogen modulated this response and resulted in higher receptor expression. In accordance, oestrogen treatment resulted in a less prominent reduction of 125I-hypercholesterolaemic VLDL clearance in the cholesterol-fed rabbits. VLDL from both groups of cholesterol-fed animals stimulated cholesteryl ester synthesis in cultured macrophages to the same extent. Thus, in rabbits under a dietary cholesterol load, oestrogen counteracted hepatic lipoprotein receptor suppression, reduced plasma VLDL- and increased plasma HDL-cholesterol levels, and to a large extent abolished the development of atherosclerosis.

Animals↗

Lipid lowering in severe familial hypercholesterolaemia: efficacy and safety of a new regenerating system for selective apheresis of apolipoprotein B-containing lipoproteins.

Preliminary experience of the efficacy and safety of a new regenerating system for selective extracorporeal removal of apolipoprotein B-containing lipoproteins is described. Four patients with familial hyperlipoproteinaemia were studied on 10 occasions. A system of two, parallel, dextran sulphate cellulose columns was used, and plasma was processed continuously by passage through one of the columns while the other was being regenerated. With this procedure, reductions of very low density and low density lipoprotein cholesterol levels by 73 and 43%, respectively, could be achieved after treatment for 2.5-3 h (1000-3200 ml of plasma volume). No clinically relevant changes in the concentrations of other plasma proteins, including high density lipoproteins, were observed, and the treatment was well tolerated. We conclude that continuous selective apolipoprotein B apheresis is a safe and efficient lipid-lowering procedure which may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.

Apolipoproteins B↗

Low CSF met-enkephalin levels in cluster headache are elevated by acupuncture.

Significantly lower met-enkephalin levels were found in CSF from cluster headache sufferers as compared to age-matched healthy volunteers, whereas it was not possible to demonstrate any clear-cut difference for beta-endorphin. CSF opioid levels may rise following manual or electroacupuncture. It was studied whether traditional Chinese (manual) acupuncture affected CSF levels of met-enkephalin or beta-endorphin in these patients, and to what extent this treatment would be beneficial for the headache. A significant rise in lumbar CSF met-enkephalin levels was found, whereas no clear change in beta-endorphin levels was obtained. The treatment was, however, of little value in preventing the headache.

Acupuncture Therapy↗

The outcome of neonatal septicemia during fifteen years.

The outcome of neonatal septicemia in 320 infants seen during 1969-83 has been evaluated. Mortality decreased from 27% to 12%. The incidence of moderate to severe handicaps in survivors remained unchanged at around 20%. Sixty percent of these handicapped children had meningitis or osteomyelitis, and many of these were healthy prior to onset. All handicapped infants without osteomyelitis or meningitis had several other risk factors that may have contributed to the final outcome.

Humans↗

Health and development of 8-year-old children whose mothers abused amphetamine during pregnancy.

Sixty-five children whose mothers were addicted to amphetamine during pregnancy were followed prospectively until eight years of age, when they were tested in their homes. Only 21 children (30%) remained in the custody of their biological mothers. Their physical health, including growth, was normal. Their IQ and their performance in several psychometric tests were within normal limits. Increased incidences of aggressive behaviour and peer-related problems were found, especially in the groups that had been exposed to amphetamine throughout pregnancy. No correlation was found with socio-environmental factors.

Amphetamine↗

Socio-economic variables and pregnancy outcome. Birthweight in singletons.

The effect of various social indicators on birthweight in singletons was studied in Sweden with the use of a medical birth registry to which census information was linked. Two years were studied: 1976 births linked to the 1975 census, and 1981 births linked to the 1980 census. The strongest social indicator affecting birthweight was family situation: whether the woman cohabited or not. After standardization for this variable, effects were still seen for occupation and type of housing. They were not secondary to maternal age or parity. By using cohabitation status, enhanced with other social indicators, two groups were selected: one privileged and one underprivileged. Distributions of birthweight and pregnancy duration in the two groups were compared with those formed in women being neither privileged nor under privileged and also working outside the home (because occupation entered the definitions of the two former groups). There were marked differences: underprivileged women had shorter pregnancy duration and, at term, their infants weighed slightly less than those of privileged women. These differences remain after standardization for maternal age and parity.

Birth Weight↗

Distribution and coexistence of corticotropin-releasing factor-, neurotensin-, enkephalin-, cholecystokinin-, galanin- and vasoactive intestinal polypeptide/peptide histidine isoleucine-like peptides in the parvocellular part of the paraventricular nucleus.

The distribution of several peptides, corticotropin-releasing factor (CRF), neurotensin (NT), enkephalin (ENK), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), cholecystokinin (CCK), thyrotropin-releasing hormone (TRH) and galanin (GAL) was studied in detail with immunohistochemistry in the various subdivisions of the parvocellular part of the rat hypothalamic paraventricular nucleus (PVN). Using a double-staining method and elution-restaining technique, the coexistence of CRF- and NT-like immunoreactivities (LI) with other neuropeptides was analyzed. Our results indicate that coexistence of two or more peptides in the PVN is common, and revealed that about 30% of the CRF neurons contain NT-LI and about 20% ENK-LI, whereas other peptides only occur in small fractions of the CRF cells. Thus, it seems possible to define three major subpopulations of CRF neurons, one containing NT-LI, another one containing ENK-LI and a third one apparently lacking these peptides. Conversely, about 60% of both NT- and ENK-immunoreactive neurons lacked CRF-LI. A large proportion of the small population of VIP/PHI neurons contained NT-LI. TRH neurons represented a neuron population completely distinct from the CRF neurons. Also, it did not seem to contain any of the other peptides studied with the rare exception of ENK-LI. Neuropeptides present in the PVN and presumably in nerve fibers of the external layer of the median eminence may participate in the control of the anterior pituitary hormone secretion. Whereas the role of CRF and TRH is well established, the physiological role of the other peptides studied here is still unclear.

Animals↗

Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma.

To characterize the effects of estrogen treatment on the metabolism of LDL we studied six males with metastatic prostatic carcinoma before and during the initiation of therapy; a repeated study was performed in five participants after 3-6 mo of treatment. The fractional catabolic rate (FCR) of autologous 125I-LDL was calculated both from elimination curves of plasma radioactivity and from urine/plasma (U/P) radioactivity ratios. Within 1-2 d of onset of estrogen therapy a more rapid decay of plasma radioactivity occurred, and FCR measured from U/P ratios increased by 20%. Concomitantly, LDL cholesterol levels decreased by 16%. After 3-6 mo of treatment FCR determined by both techniques was almost doubled, and LDL cholesterol was reduced by 34%. This occurred despite a 29% increase in the calculated synthesis rate of LDL. Tissue culture studies demonstrated that the receptor affinity of LDL isolated from patients on long-term estrogen therapy was reduced. We conclude that a profound increase in LDL catabolism is induced through administration of pharmacological doses of estrogen in males, and hypothesize that this is the consequence of an increased expression of hepatic LDL receptors. This enhanced catabolism of LDL leaves LDL particles in plasma with lower affinity for the LDL receptor.

Aged↗

Colonization with potentially pathogenic respiratory tract bacteria. A household study.

A group of 235 persons (180 adults and 55 children 0-15 years old) recorded symptoms of upper respiratory tract infection daily during two three-month periods (autumn 1986 and spring 1987). Samples for culture were taken from the nasopharynx and throat once during each period. Fifteen per cent of asymptomatic subjects harboured respiratory pathogens in the nasopharynx, as did 28% of those subjects with minor respiratory tract infections and 46% of those with more severe respiratory tract infections. Of children up to seven years of age, 58% were colonized with potential respiratory pathogens, which is important to keep in mind when evaluating culture reports from young children. Adults living with young children were colonized significantly more often than other adults. Branhamella catarrhalis was the most common pathogen.

Adolescent↗

Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.

Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.

Acute Kidney Injury↗

Anthracycline-DNA interactions studied with linear dichroism and fluorescence spectroscopy.

DNA-binding geometry and dynamics of a number of anthracyclines, including adriamycin and 4-demethoxydaunorubicin, interacting with DNA have been studied by means of linear dichroism and fluorescence techniques. The anthracycline chromophore is found to be approximately parallel to the plane of the DNA bases and to have a restricted mobility, as would be expected for an intercalative binding mode, but there are variations between different directions in the chromophore as well as between the drugs. From dichroic spectra of adriamycin in an anisotropic host of poly(vinyl alcohol), absorption components corresponding to transitions with mutually orthogonal polarizations have been resolved. These can be exploited to determine the orientations of the two chromophore axes in the DNA complex relative to the DNA helix axis. In a certain binding regime the long axis of the bound anthracycline chromophores (with the exception of 4-demethoxydaunorubicin) is found to be approximately 10 degrees closer to perpendicular to the helix axis than are the DNA bases. This demonstrates that the average base tilt is at least 10 degrees. By contrast, the short axis of the aglycon moiety is found to be tilted some 20-30 degrees from perpendicular. This may be because it is probing a base direction with a more pronounced, static or dynamic, inclination than the average in DNA. The drug orientation and the DNA orientation (reflecting flexibility) are observed to vary differently and nonmonotonically with binding ratio, suggesting specific binding and varying site geometries.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotics, Antineoplastic↗

The association between soft tissue sarcomas and exposure to phenoxyacetic acids. A new case-referent study.

A case-referent study on soft tissue sarcomas (STS) was conducted, to see if previous findings regarding an association between exposure to phenoxyacetic acids or chlorophenols and this tumor type could be reproduced. Fifty-five male STS patients were thereby compared with 220 living and 110 dead population-based referents. Furthermore, another referent group consisting of 190 patients with another type of malignant disease was used in order to evaluate any influence of recall bias on the results. To obtain information about exposure to the studied chemicals, as well as about any other exposures that might be of interest, questionnaires were used, and if necessary these were completed over the phone by an interviewer who had no information regarding case-referent status. All analysis and interpretation of exposure data were done in a blinded manner. Exposure to phenoxyacetic acids gave a roughly three-fold increased risk for STS, thereby confirming previous findings, whereas exposure to chlorophenols was not associated with STS in this study.

Adult↗

Structural properties of the covalent (+)-anti-BPDE-poly(dG-dC)(dG-dC) complex.

The structure of the covalent (+)-anti-BPDE-poly(dG-dC) complex can be represented by two preferred orientations of the pyrene moiety; one at about 20 degrees relative to the helix axis and one at about 70 degrees, populated as 4:1. A rapid mobility of the BPDE may allow an exchange between the two orientations. The poly(dG-dC) structure becomes more flexible by (+)-anti-BPDE modification, seen as a shortened persistence length. This complex may be significant as a model for DNA interaction with covalently binding polyaromatic carcinogens.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗