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Biomedical subjects

J C Hansen

Publications and source records attributed to J C Hansen.

At least 91 records · Page 5Linked to original sources
PubMed1992

Influence of chromatin folding on transcription initiation and elongation by RNA polymerase III.

Nucleosomes were assembled onto either closed circular plasmids containing a single Xenopus 5S RNA gene or a linear tandemly repeated array of Lytechinus 5S RNA genes. Both chromatin templates were found to vary in their extent of compaction, depending upon the type and concentration of cation in solution. Compaction of these chromatin templates led to a significant inhibition of both transcription initiation and elongation by RNA polymerase III. Thus, the transcriptional repression observed after incorporation of genes into chromatin depends not only on occlusion of the promoter elements through direct contact with histones but also on compaction of nucleosomal arrays which occurs under the conditions of the transcription reactions.

Animals↗
PubMed1992

Chromatin dynamics and the modulation of genetic activity.

Chromatin, the genetic material of eukaryotes, is a dynamic macromolecular assembly that continuously changes its composition and conformation to accommodate different stages of genetic activity, e.g. transcription and replication. Evidence is accumulating that the dynamic behavior of chromatin has important functional roles in the modulation of genetic activity, largely due to the intrinsic properties of arrays of nucleosome cores.

Animals↗
PubMed1992

Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antioxidative response to selenium supplementation in polymorphonuclear leucocytes.

The antioxidant capacity of the glutathione redox cycle and the concentrations of selenium in serum, red blood cells or whole blood, and polymorphonuclear leucocytes was evaluated in nine patients with severe rheumatoid arthritis (RA) and eight healthy controls receiving daily supplementation with 250 micrograms selenomethionine for six months. Serum and whole blood concentrations of selenium and the activity of the selenium dependent enzyme glutathione peroxidase (GSH-Px) were low in the serum, red blood cells, and polymorphonuclear leucocytes of patients with RA before selenium supplementation. During supplementation serum and whole blood concentrations of selenium and the activity of GSH-Px in serum and red blood cells of patients with RA and serum GSH-Px in controls increased. Selenium and GSH-Px in polymorphonuclear leucocytes were unaffected in patients with RA in contrast with the controls where both were augmented. Glutathione reductase activity in the red blood cells and polymorphonuclear leucocytes of patients with RA was low but increased during selenium supplementation. Whole blood concentrations of glutathione were slightly lower in patients with RA than controls and no difference in the content in polymorphonuclear leucocytes was found between the groups. The activity in red blood cells of glucose-6-phosphate dehydrogenase was high in patients with RA, indicating sufficient function of the hexose monophosphate pathway. The reduced antioxidant activity of the glutathione redox cycle in patients with severe RA was mainly due to the low availability of selenium. This was further supported by the response to selenium supplementation in serum and red blood cells. In the polymorphonuclear leucocytes, however, no biochemical effects of selenium supplementation were seen. This lack of antioxidative response could play a pathogenetic part in inflammation in patients with RA.

Adult↗
PubMed1992

Serum ferritin in a Greenlandic Inuit hunter population from the Thule district.

Serum (S-) ferritin was analyzed in 67 Greenlandic Inuit hunters from Thule (Qaanaaq), 35 males and 32 females with a median age of 39 years (range 17-77). S-ferritin was higher in males, median 211 micrograms/l (range 30-1040), than in females, median 87 micrograms/l (range 33-794) (p less than 0.01). None of the subjects had S-ferritin less than or equal to 20 micrograms/l (i.e. depleted iron stores); 5 of the 48 subjects less than or equal to 50 years old had S-ferritin 21-40 micrograms/l (i.e. small iron stores). All 19 subjects greater than 50 years old had S-ferritin greater than 40 micrograms/l (i.e. replete iron stores) and 8 showed values greater than 300 micrograms/l (i.e. increased iron stores). S-ferritin levels increased with the percent energy intake from traditional native hunter food (rs = 0.26, p less than 0.05). Inuit had higher S-ferritin than Danish Caucasian subjects. In Inuit of both sexes, S-ferritin displayed a correlation to age (rs = 0.63, p less than 0.0001 in the entire series), indicating gradually increasing S-ferritin levels during lifetime, without the plateaus seen in Caucasians. These findings suggest continued accumulation of iron reserves in elderly Inuit, due to consumption of large quantities of iron rich meat from marine mammals and/or genetic differences in the regulatory mechanisms for body iron stores.

Adolescent↗
PubMed1991

The mechanism of nucleosome assembly onto oligomers of the sea urchin 5 S DNA positioning sequence.

We have used a model system composed of tandem repeats of Lytechinus variegatus 5 S rDNA (Simpson, R. T., Thoma, F., and Brubaker, J. M. (1985) Cell 42, 799-808) reconstituted into chromatin with chicken erythrocyte core histones to investigate the mechanism of chromatin assembly. Nucleosomes are assembled onto the DNA template by mixing histone octamers and DNA in 2 M NaCl followed by stepwise dialysis into very low ionic strength buffer over a 24-h period. By 1.0 M NaCl, a defined intermediate composed of arrays of H3.H4 tetramers has formed, as shown by analytical and preparative ultracentrifugation. Digestion with methidium propyl EDTA.Fe(II) indicates that these tetramers are spaced at 207 base pair intervals, i.e. one/repeat length of the DNA positioning sequence. In 0.8 M NaCl, some H2A.H2B has become associated with the H3.H4 tetramers and DNA. Surprisingly, under these conditions DNA is protected from methidium propyl EDTA.Fe(II) digestion almost as well as in the complete nucleosome, even though these structures are quite deficient in H2A.H2B. By 0.6 M NaCl, nucleosome assembly is complete, and the MPE digestion pattern is indistinguishable from that observed for oligonucleosomes at very low ionic strength. Below 0.6 M NaCl, the oligonucleosomes are involved in various salt-dependent conformational equilibria: at approximately 0.6 M, a 15% reduction in S20,w that mimics a conformational change observed previously with nucleosome core particles; at and above 0.1 M, folding into a more compact structure(s); at and above 0.1 M NaCl, a reaction involving varying amounts of dissociation of histone octamers from a small fraction of the DNA templates. In low ionic strength buffer (less than 1 mM NaCl), oligonucleosomes are present as fully loaded templates in the extended beads-on-a-string structure.

Animals↗
PubMed1991

Short-term group interventions for mentally ill young adults living in a community residence and their families.

Data from 12 families of chronic mentally ill young adults who were living in a supportive residential facility were used to compare the effects on family functioning of a multiple-family psychoeducational group and a multiple-family support group. The psychoeducational group provided information about mental illness and family dynamics and taught effective communication and conflict management skills. The support group consisted of unstructured discussions about topics raised by the families. Both groups met once a week for five weeks and included both parents and their mentally ill adult children. The emotional climate, level of organization, and other aspects of the family environment were assessed before and after treatment and at three-month follow-up. Both groups helped families to become more cohesive, to manage conflict more effectively, and to obtain a greater internal locus of control.

Adaptation, Psychological↗
PubMed1991

Effects of amrinone on thrombin-induced platelet-derived growth factor-like protein secretion from endothelial cells.

Endothelial cells (EC) secrete platelet-derived growth factor (PDGF)-like protein, which is a potent mitogen to smooth muscle and connective tissue cells. The purpose of this study was to determine if amrinone, a phosphodiesterase inhibitor, could inhibit PDGF-like protein secretion on the basis of its ability to increase cAMP. Human umbilical artery endothelial cells (HUAEC) (n = 7) were preincubated for 4 h with amrinone (10 micrograms/mL) before coincubation with thrombin (10 IU/mL) and amrinone (10 micrograms/mL) for 18 h. The supernatant was then assayed for the presence of both PDGF-like protein by using a competitive 125I-PDGF radioreceptor inhibition assay, and cAMP by using an RIA. Thrombin-induced PDGF-like protein secretion from HUAEC was significantly inhibited by amrinone (7.8 +/- 1.6 fmol/10(6) EC) when compared with thrombin alone (12.1 +/- 2.4 fmol/10(6) EC) (p less than 0.05). Amrinone alone had no effect on baseline PDGF-like protein secretion. Amrinone inhibition of thrombin-induced PDGF-like protein secretion was comparable whether amrinone was added to HUAEC 4 or 0 h before thrombin, and it was dose dependent with a maximal inhibition of 82.7% by amrinone (160 micrograms/mL). In contrast, IL-1 alpha (10 micrograms/mL) and tumor necrosis factor (100 ng/mL) induced less secretion of PDGF-like protein from HUAEC, and this secretion was not inhibited by amrinone. Amrinone (10 micrograms/mL) significantly increased secretion of cAMP from HUAEC from a baseline value of 6.4 +/- 0.4 pmol/10(6) EC to 10.6 +/- 0.1 pmol/10(6) EC (p less than 0.01). We conclude that amrinone inhibits thrombin-induced PDGF-like protein secretion from HUAEC.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗
PubMed1990

High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium.

High-dose antioxidant supplementation has recently been recommended for multiple sclerosis (MS) patients. This study tests the clinical safety, the glutathione peroxidase (GSH-px) activity, and the absorption of selenium during such supplementation. Eighteen MS patients were given 6 tablets especially made for this study, equivalent to 6 mg sodium selenite, 2 g vitamin C, and 480 mg vitamin E a day for five wk. GSH-px, which was lower than in non-MS controls before the start of treatment, increased fivefold during 5 wk of treatment. Side effects were scarce. Ten MS patients were subjected to a 24-h selenium absorption study after ingestion of 2 active tablets, equivalent to 2 mg sodium selenite. Selenium, which was low initially, increased 24% during the first 3 h and then stabilized. It is concluded that the tested antioxidant treatment seems to be safe and that MS patients have low GSH-px, which may be increased by the tested antioxidant treatment.

Absorption↗
PubMed1990

DNA and protein determinants of nucleosome positioning on sea urchin 5S rRNA gene sequences in vitro.

DNA and protein determinants of nucleosome positioning have been examined after in vitro reconstitutions of native or modified histone octamers onto tandem repeats of 207- and 172-base-pair DNA sequences containing the Lytechinus variegatus 5S rRNA gene and onto monomeric sequences derived from these by digestion with various restriction endonucleases. In all cases, a major nucleosome position as well as a number of minor positions have been observed, which indicates that the generation of multiple positions is an inherent property of the 5S rRNA gene sequence. Interestingly, all positions observed differ by multiples of 10 base pairs. Data obtained under different reconstitution conditions demonstrate that the observed distributions of nucleosomes on these DNA templates are equilibrium distributions. This study has also examined the positioning of histone octamers from which histone "tails" had been removed by tryptic digestion. Results indicate that the histone tails are not determinants of nucleosome positioning. Although our results suggest that the mechanical properties of the 5S rDNA are the fundamental factors determining nucleosome positioning, they are insufficient to direct all nucleosomes into a single location.

Animals↗
PubMed1990

Dietary intake of methylmercury as a correlate of gestational length and birth weight among newborns in Greenland.

Between January 1983 and December 1986, a total of 376 mothers living in Godthaab and Thule, Greenland, were asked about their average weekly intake of marine food. The blood methylmercury concentrations of mothers and offspring were measured. Mean methylmercury concentrations in infants were found to be 40 percent higher than in mothers. High maternal and offspring methylmercury blood concentrations were found to be associated with low mean birth weight, but not with short gestational length.

Adolescent↗
PubMed1989

Homogeneous reconstituted oligonucleosomes, evidence for salt-dependent folding in the absence of histone H1.

Using the method of salt dialysis, we have reconstituted histone octamers onto DNA templates consisting of 12 tandem repeats, each containing a fragment of the sea urchin 5S rRNA gene [Simpson, R.T., Thoma, F., & Brubaker, J.M. (1985) Cell 42, 799-808]. In these templates, each sea urchin repeat contains a sequence for preferred nucleosome positioning. Sedimentation velocity and sedimentation equilibrium studies in the analytical ultracentrifuge indicate that at molar histone/DNA ratios of 1.0-1.1 extremely homogeneous preparations of fully loaded oligonucleosomes (12 nucleosomes/template) can be regularly obtained. Digestion of the oligonucleosomes with micrococcal nuclease, followed by restriction mapping of purified nucleosome-bound DNA sequences, yields a complicated but consistent pattern of nucleosome positioning. Roughly 50% of the nucleosomes appear to be phased at positions 1-146 of each repeat, while the remainder of the nucleosomes occupy a number of other minor discrete positions along the template that differ by multiples of 10 bp. From sedimentation velocity studies of the oligonucleosomes in 0-0.2 M NaCl, we observe a reversible increase in mean sedimentation coefficient by almost 30%, accompanied by development of heterogeneity in sedimentation. These results, in combination with theoretical predictions, indicate that linear stretches of chromatin in the absence of lysine-rich histones exist in solution in a salt-dependent equilibrium between an extended (low salt) conformation and one or more folded (high salt) structures. In addition, by 100 mM NaCl, salt-dependent dissociation of histone octamers from these linear oligonucleosomes is observed.

Animals↗
PubMed1989

Large-scale purification of plasmid insert DNA sequences using low-percentage agarose exclusion chromatography.

Linear double-stranded DNA fragments ranging from 0.14 to 8.4 kbp have been fractionated on low-percentage agarose exclusion gels. Both Ultragel A2 (2% agarose) and Bio-Gel A150m (1% agarose) exclude DNA fragments greater than 900 bp, while the exclusion limit of Bio-Gel A50m (2% agarose) is about 350 bp. All gels result in moderate resolution of DNA fragments smaller than the exclusion limits; we generally observe nearly complete one-step separation of fragments that differ in size by a factor of 2. On the basis of these results, we have used these exclusion gels to routinely purify greater than 0.4 mg of plasmid insert DNA sequences in one step and over 2.5 mg with a single column, demonstrating that these gel matrices can be ideally suited for repeated rapid large-scale purification of plasmid inserts. In addition, this knowledge allows for a more rational design of plasmids in those cases where large-scale use of the insert DNA is required.

Chromatography, Agarose↗
PubMed1989

Kinetics and in vitro origin of the temperature-dependent transition of the estrogen receptor monomer.

Partitioning of estrogen receptors in aqueous two-phase polymer systems has provided the basis for a detailed kinetic analysis of the effects of temperature on estrogen receptor (ER) structure in vitro. Exposure to temperatures of 0-30 degrees C increased the rate of change in ER partition coefficients by up to 100-fold but did not affect the final extent of the process. The temperature-dependent change in ER partition coefficients was characterized by a linear Arrhenius plot and an activation energy of 25 kcal/mol. The rate of the temperature-dependent ER transition (28 degrees C) was found to be unaffected by greater than 50-fold changes in receptor concentration, which indicates that the temperature-dependent change in partition coefficients reflects a first-order process. The partition coefficients of heated ER were unaffected by subsequent 18-h incubations at 0 degree C, indicating that the temperature-dependent ER transition is irreversible in vitro. Direct heating of the unoccupied ER resulted in both a change in ER partition coefficients and a loss of ER binding sites. The temperature-dependent change in unoccupied ER partition coefficients was complete within 30 min at 28 degrees C and yielded a first-order rate constant that was the same as that obtained for heating the receptor-estradiol complex at 28 degrees C. In contrast, the loss of unoccupied ER binding sites that occurred during 28 degrees C incubations did not reach completion after 150 min of heating and was found to behave as a second-order process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Distribution of dietary mercury in a dog. Quantitation and localization of total mercury in organs and central nervous system.

An Alsatian dog which had been fed fish contaminated with methyl mercury for 7 years was examined after its death at the age of 12, 4 years after the exposure to methyl mercury had ceased. Two dogs of the same age and breed served as controls. In the exposed dog, mercury was found in all of the organs examined; the highest concentrations were found in the kidneys, and the lowest in the gastrointestinal tract and skeletal muscles. In the central nervous system (CNS) the mercury was fairly uniformly distributed, with 93% in the inorganic state, whereas the skeletal muscles contained approximately 30% inorganic mercury. This demonstrates time-dependent demethylation and suggests a variation in the rate from one type of tissue to another. At the time of death, the mercury level in the dog was still falling. In the control dogs, detectable amounts (0.01 mg kg-1) of mercury were only found in the kidney and liver. The distribution of mercury was determined by a histochemical method (autometallography) for locating mercury in tissue sections. Sections from autometallography of the central nervous system showed large deposits of mercury in all areas of the cerebral hemispheres, the brainstem and the spinal cord, including nerve cells, astrocytes, microglial cells and vessel walls. The granular layer of the cerebellar hemispheres was especially loaded, while only a few granules were present in the Purkinje cells. In the leptomeninges the vessels and the macrophages were heavily encrusted. High amounts of histochemically demonstrable mercury were observed in the liver, thyroid gland and kidney. In the control dogs, all the organs examined were practically devoid of deposits.

Animals↗
PubMed1989

Selenium in rheumatoid arthritis. A historical prospective approach.

Time-dependent changes in serum selenium concentrations were studied in 28 patients with rheumatoid arthritis and the concentrations were related to disease activity. The mean length of the observation period was 7.3 years and a mean of 6 analyses was performed for each patient. Serum selenium fluctuated with disease activity in most patients and a relatively low concentration was recorded in periods of high disease activity. Gold treatment had no influence on the selenium concentrations and selenium levels measured within the first year of the disease were not demonstrated to have any prognostic significance.

Arthritis, Rheumatoid↗