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J C Hansen

Publications and source records attributed to J C Hansen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of contaminants from different trophic levels and ecosystems.

The present paper provides an overview of the priority contaminants and media from the Greenland part of the Arctic Monitoring and Assessment Program. Levels and accumulation patterns of heavy metals, POPs and a radionuclide (137Cs) are compared from the terrestrial, freshwater and marine ecosystems. Of the nine compounds presented, seven (Cd, Hg, Se, sigma PCB, sigma DDT, sigma HCH, HCB) increased in concentration towards higher trophic levels. For these contaminants the concentrations in soil and aquatic sediment were in the same order of magnitude, whereas the concentrations in marine biota were higher than found in the freshwater and terrestrial ecosystems probably due to the presence of longer food chains. Pb and 137Cs showed the reverse pattern compared with the other compounds. The concentrations in soil and aquatic sediments decreased in the order terrestrial, freshwater and marine ecosystems, which was reflected in the biota as well. Reindeer had similar or lower levels of Pb and 137Cs than lichens. Levels of Pb and 137Cs in marine biota did not show the same clear increase towards higher trophic as found for the other analysed compounds. Greenland Inuit contains considerably less mercury but higher levels of sigma PCB, sigma DDT and HCB than other Arctic marine top consumers.

Animals↗
PubMed2000

Elements in autopsy liver tissue samples from Greenlandic Inuit and Danes. II. Iron measured by X-ray fluorescence spectrometry.

The purpose of this study was to measure the content of iron (Fe) in liver tissue samples from urbanized Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver tissue samples from urbanized Danes. Normal liver tissue samples were obtained at autopsy from 50 Greenlandic Inuit (27 men, 23 women) with a median age of 61 years (range 23-83) and from 72 Danes (42 men, 30 women) with a median age of 62 years (range 15-87). In the entire series, there was no significant difference between liver iron in Inuit compared with Danes. Likewise, there was no significant gender difference concerning liver iron content, either in Inuit or in Danes. The median iron content (with 5-95 percentile) in Inuit was 17.23 mmol/kg dry liver (5.80-91.80) and in Danes 16.51 mmol/kg dry liver (7.83-39.05). However, when stratified according to age, a trend was revealed showing that Inuit men and women < or = 50 years had a lower liver iron content than Danes (p = 0.05 and p = 0.08) whereas Inuit men and women > 50 years had a higher liver iron content than Danes (p = 0.18 and p = 0.02). There was a significant correlation between liver iron content and age in both Inuit men (rs = 0.49, p = 0.01) and in women (rs = 0.64, p = 0.003), but not in Danes. In Inuit, the median hepatic iron index (liver iron content divided by age) was 0.33 in men and 0.32 in women. The median estimated iron content in the whole liver was 6.54 mmol (365 mg) in Inuit men and 5.41 mmol (302 mg) in Inuit women (p = 0.6). There was no correlation between hepatic iron index and age. In Danes, the median hepatic iron index was 0.46 in men and 0.29 in women (p = 0.01). There was a significant inverse correlation between hepatic iron index and age in the two genders and in the entire series (rs = -0.71, p = 0.0001). The results indicate that young and middle-aged urbanized Inuit have slightly smaller iron stores than urbanized Danes, whereas elderly Inuit have higher iron stores than Danes. In Danes, iron stores plateau at 30 to 40 years of age in men and some years after the menopause in women. In Inuit, iron stores continue to increase in old age, probably to due a lifelong dietary intake of haem iron.

Adolescent↗
PubMed2000

Role of histone acetylation in the assembly and modulation of chromatin structures.

The acetylation of the core histone N-terminal "tail" domains is now recognized as a highly conserved mechanism for regulating chromatin functional states. The following article examines possible roles of acetylation in two critically important cellular processes: replication-coupled nucleosome assembly, and reversible transitions in chromatin higher order structure. After a description of the acetylation of newly synthesized histones, and of the likely acetyltransferases involved, an overview of histone octamer assembly is presented. Our current understanding of the factors thought to assemble chromatin in vivo is then described. Genetic and biochemical investigations of the function the histone tails, and their acetylation, in nucleosome assembly are detailed, followed by an analysis of the importance of histone deacetylation in the maturation of newly replicated chromatin. In the final section the involvement of the histone tail domains in chromatin higher order structures is addressed, along with the role of histone acetylation in chromatin folding. Suggestions for future research are offered in the concluding remarks.

Acetylation↗
PubMed2000

High human plasma levels of organochlorine compounds in Greenland. Regional differences and lifestyle effects.

INTRODUCTION: The purpose of the study has been to analyse data, collected for surveillance purposes under the Human Health Programme of AMAP (Arctic Monitoring and Assessment Programme, in Greenland, regarding geographical differences and lifestyle versus pollution load from persistent organic pollutants (POP), and to make possible exposure assessments. It comprises a regional study from six districts and an ongoing study of pregnant women and infants. METHODOLOGY: Biostatistical analyses of data collected in Greenland from 61 men and 10 women from six different districts (1997-98) and from 110 mother-infant pairs in the Disko Bay area (1996-97) and 223 mother-infant pairs (1994-96). The data consisted of questionnaire answers and bloodsamples from men, women, and newborn infants (cord blood) analysed for fatty acids, selenium and 26 POPs including 14 PCB-congeners and four toxaphenes. RESULTS: Strong regional differences were found, related to different intakes of marine food with very high PCB-loads among men from the East coast. The various POP-plasma levels were mutually correlated and strong correlations were found between POP-plasma concentrations in mothers and new-born, R > 0.9, p < 0.0001. Among the pregnant women 95% surpassed the Canadian concern level for PCB, and 60% of the men from Scoresbysund surpassed the action level. The association between reported monthly food frequency and POPs was relatively weak, but the POPs were strongly correlated with plasma and erythrocyte n-3/n-6 fatty acid ratios as biomarkers of marine food intake. Multiple regression analysis showed highly significant positive correlation between smoking, and POP-plasma levels, after correction for age, alcohol intake, marine food, plasma lipids and n-3/n-6 fatty acid ratios. CONCLUSION: As the most important determinants of high POP-plasma levels in Greenlanders we propose: age, high plasma n-3 fatty acids (marine food), East coast region, and being a smoker.

Adult↗
PubMed1999

Functional interaction between GCN5 and polyamines: a new role for core histone acetylation.

Polyamines are organic polycations essential for a wide variety of cellular functions, including nuclear integrity and chromosome condensation. Here we present genetic evidence that depletion of cellular polyamines partially alleviates the defects in HO and SUC2 expression caused by inactivation of the GCN5 histone acetyltransferase. In addition, the combination of polyamine depletion and a sin(-) allele of the histone H4 gene leads to almost complete bypass of the transcriptional requirement for GCN5. In contrast, polyamine depletion does not alter the transcriptional requirements for the SWI/SNF chromatin remodeling complex nor does depletion lead to global defects in transcriptional regulation. In addition to these genetic studies, we show that polyamines facilitate oligomerization of nucleosomal arrays in vitro, and that polyamine-mediated condensation requires intact core histone N-terminal domains and is inhibited by histone hyperacetylation. Our studies suggest that polyamines are repressors of transcription in vivo, and that one role of histone hyperacetylation is to antagonize the ability of polyamines to stabilize highly condensed states of chromosomal fibers.

Acetylation↗
PubMed1999

The core histone N-terminal domains are required for multiple rounds of catalytic chromatin remodeling by the SWI/SNF and RSC complexes.

SWI/SNF and RSC are large, distinct multi-subunit complexes that use the energy of ATP hydrolysis to disrupt nucleosome structure, facilitating the binding of transcription factors or restriction enzymes to nucleosomes [Cote, J., Quinn, J., Workman, J. L., and Peterson, C. L. (1994) Science 265, 53-60 (1); Lorch, Y., Cairns, B. R., Zhang, M., and Kornberg, R. D. (1998) Cell 94, 29-34 (2)]. Here we have used a quantitative assay to measure the activities of these ATP-dependent chromatin remodeling complexes using nucleosomal arrays reconstituted with hypoacetylated, hyperacetylated, or partially trypsinized histones. This assay is based on measuring the kinetics of restriction enzyme digestion of a site located within the central nucleosome of a positioned 11-mer array [Logie, C., and Peterson, C. L. (1997) EMBO J. 16, 6772-6782 (3)]. We find that the DNA-stimulated ATPase activities of SWI/SNF and RSC are not altered by the absence of the histone N-termini. Furthermore, ATP-dependent nucleosome remodeling is also equivalent on all three substrate arrays under reaction conditions where the concentrations of nucleosomal array and either SWI/SNF or RSC are equivalent. However, SWI/SNF and RSC cannot catalytically remodel multiple nucleosomal arrays in the absence of the histone termini, and this catalytic activity of SWI/SNF is decreased by histone hyperacetylation. These results indicate that the histone termini are important for SWI/SNF and RSC function; and, furthermore, our data defines a step in the remodeling cycle where the core histone termini exert their influence. This step appears to be after remodeling, but prior to intermolecular transfer of the remodelers to new arrays.

Acetylation↗
PubMed1999

High serum coenzyme Q10, positively correlated with age, selenium and cholesterol, in Inuit of Greenland. A pilot study.

Greenlanders (Eskimos) have low prevalence of ischaemic heart disease, partly explained by a lower extent of atherosclerosis and a low n-6/n-3 ratio of polyunsaturated fatty acids. As atherosclerosis is also a result of oxidative stress, the total antioxidative readiness could have a substantial impact. From a health survey we chose the subpopulation from the most remote area, where the traditional Greenlandic diet with high intake of sea mammals and fish predominates. The mean (SD) of S-CoQ10 in males was 1.495 (0.529) nmol/ml and 1.421 (0.629) nmol/ml in females, significantly higher (p < 0.001) compared to a Danish population. In a linear multiple regression model the S-CoQ10 level is significantly positively associated with age and S-selenium in males, and S-total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place, and it could probably be a substantial part of the antioxidative defense.

Adult↗
PubMed1999

Internal carotid artery patency following common carotid artery occlusion: management of the asymptomatic patient.

Rarely, internal carotid artery (ICA) patency is maintained above a common carotid artery occlusion (CCAO) through collateral flow of the ipsilateral external carotid artery or an aberrant ICA branch. Several small series report excellent results of ICA revascularization in relieving cerebral ischemic symptoms in these patients. The natural history of CCAO with patent ICA in the asymptomatic patient, however, is unknown. The Greenville Memorial Hospital Vascular Teaching Service registry and all carotid duplex scans done in the Greenville Hospital System vascular laboratory from January 1994 through December 1997 were reviewed. Data collection included chart review, phone interviews, and the review of angiograms and duplex scans. This study suggests that carotid duplex is more sensitive for detecting ICA flow after CCAO than routine contrast angiography. It also suggests that while rare in presentation, asymptomatic patients with CCAO and a patent ICA appear to have a benign neurologic course and can probably be observed without a high risk of stroke.

Carotid Artery, Common↗
PubMed1999

Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland.

Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher than those measured using the same analytical method in samples from Canadians in Quebec City, Quebec. Brain lipids contained lower concentrations of all organochlorines than lipids extracted from other tissues. Organochlorine residue levels in lipid extracts from liver, omental fat, and subcutaneous abdominal fat samples were similar, with the exception of ss-hexachlorocyclohexane, which reached a greater concentration in liver lipids than in lipids from both adipose tissues (4-fold; p < 0. 05). Comparisons with available international data on adipose tissue levels reveal that the organochlorine body burden in the Inuit population of Greenland is presently among the highest resulting from environmental exposure.

Adipose Tissue↗
PubMed1999

Mercury accumulations in brains from populations exposed to high and low dietary levels of methyl mercury. Concentration, chemical form and distribution of mercury in brain samples from autopsies.

Autopsy samples from 17 Greenlanders and 12 Danes were analysed for total and organic mercury by atomic absorption spectrophotometry, and for cellular localisation by autometallography. The concentration of total mercury in the Greenlanders (median: 174 micrograms Hg/kg wet weight brain tissue, range 59-4782, highest in cerebellum: 492) was found to be significantly higher than in the Danish group (3.7 micrograms Hg/kg w.w., range 1.2-11.8). Furthermore, the total concentration of mercury was positively correlated to age (rho = 0.56, p < 0.05), and the fraction of methyl mercury was negatively correlated to age (rho = -0.66, p < 0.01) among the Greenlanders. This suggests an age dependent accumulation of total mercury and a slow transformation of methyl mercury to inorganic mercury in the brain. The autometallographically demonstrable mercury was primarily located in glia cells.

Adult↗
PubMed1999

High blood levels of persistent organic pollutants are statistically correlated with smoking.

Persistent Organic Pollutants (11 pesticides and 14 PCB-congeners), and heavy metals (Cd, Cu, Hg, Pb, Se, and Zn) were determined in 175 pregnant women and 160 newborn infants (umbilical cord blood) from Disko Bay, Greenland, 1994-96. Among these, 135 women filled out questionnaires about drinking, smoking and intake of traditional Inuit food. Multiple linear regression analyses showed highly significant positive associations between the mothers' smoking status (never, previous, present) and plasma concentrations of all the studied organic pollutants both in maternal blood and umbilical cord blood. Traditional food and not the tobacco is known to be the source of the contaminants. But smoking may influence the enzymatic turnover of toxic substances.

Adolescent↗
PubMed1998

Structure and function of the core histone N-termini: more than meets the eye.

For two decades, the core histone N-termini generally have been thought of as unstructured domains whose function is to bind to DNA and screen negative charge. New data indicates that both the molecular mechanisms of action and biological functions of the core histone N-termini in chromatin are considerably more complex. At the level of the chromatin fiber, multiple distinct functions of the N-termini are required to achieve higher order chromatin condensation, two of which apparently involve protein-protein rather than protein-DNA interactions. In addition, the N-termini have been documented to participate in specific interactions with many chromatin-associated regulatory proteins. Here, we discuss evidence supporting the new concepts that when functioning in their natural chromatin context, (1) the N-termini are engaged primarily in protein-protein interactions, (2) as a consequence of these interactions the N-termini adopt specific secondary structure, (3) posttranslational modifications such as acetylation disrupt the ability of the N-termini to form secondary structure, and (4) because the N-termini perform essential roles in both chromatin condensation and also bind specific chromatin-associated proteins, the global structure and function of any given region of the genome will be determined predominantly by the core histone N-termini and their specific interaction partners.

Amino Acid Sequence↗
PubMed1998

Gcn5p, a transcription-related histone acetyltransferase, acetylates nucleosomes and folded nucleosomal arrays in the absence of other protein subunits.

Gcn5p is the catalytic subunit of several type A histone acetyltransferases (HATs). Previous studies performed under a limited range of solution conditions have found that nucleosome core particles and nucleosomal arrays can be acetylated by Gcn5p only when it is complexed with other proteins, e.g. Gcn5-Ada, HAT-A2, and SAGA. Here we demonstrate that when assayed in buffer containing optimum concentrations of either NaCl or MgCl2, purified yeast recombinant Gcn5p (rGcn5p) efficiently acetylates both nucleosome core particles and nucleosomal arrays. Furthermore, under conditions where nucleosomal arrays are extensively folded, rGcn5p acetylates folded arrays approximately 40% faster than nucleosome core particles. Finally, rGcn5p polyacetylates the N termini of free histone H3 but only monoacetylates H3 in nucleosomes and nucleosomal arrays. These results demonstrate both that rGcn5p in and of itself is catalytically active when assayed under optimal solution conditions and that this enzyme prefers folded nucleosomal arrays as a substrate. They further suggest that the structure of the histone H3 N terminus, and concomitantly the accessibility of the H3 acetylation sites, changes upon assembly into nucleosomes and nucleosomal arrays.

Acetylation↗
PubMed1998

Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin.

The compaction level of arrays of nucleosomes may be understood in terms of the balance between the self-repulsion of DNA (principally linker DNA) and countering factors including the ionic strength and composition of the medium, the highly basic N termini of the core histones, and linker histones. However, the structural principles that come into play during the transition from a loose chain of nucleosomes to a compact 30-nm chromatin fiber have been difficult to establish, and the arrangement of nucleosomes and linker DNA in condensed chromatin fibers has never been fully resolved. Based on images of the solution conformation of native chromatin and fully defined chromatin arrays obtained by electron cryomicroscopy, we report a linker histone-dependent architectural motif beyond the level of the nucleosome core particle that takes the form of a stem-like organization of the entering and exiting linker DNA segments. DNA completes approximately 1.7 turns on the histone octamer in the presence and absence of linker histone. When linker histone is present, the two linker DNA segments become juxtaposed approximately 8 nm from the nucleosome center and remain apposed for 3-5 nm before diverging. We propose that this stem motif directs the arrangement of nucleosomes and linker DNA within the chromatin fiber, establishing a unique three-dimensional zigzag folding pattern that is conserved during compaction. Such an arrangement with peripherally arranged nucleosomes and internal linker DNA segments is fully consistent with observations in intact nuclei and also allows dramatic changes in compaction level to occur without a concomitant change in topology.

Animals↗