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Biomedical subjects

J C Hansen

Publications and source records attributed to J C Hansen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Influence of dosage and timing of application of platelet-derived growth factor on early healing of the rat medial collateral ligament.

In previous studies, platelet-derived growth factor has demonstrated beneficial in vivo effects on wound healing. We report the results of two studies of platelet-derived growth factor in the rat medial collateral ligament injury model. Experimental injury sites were implanted with platelet-derived growth factor, whereas contralateral controls received only collagen. Twelve days postoperatively, the femur-medial collateral ligament-tibia complex was tested mechanically. Our first study found a marked drop in the effectiveness of platelet-derived growth factor when it was administered more than 24 hours after injury. Dose-response testing showed maximum increases in strength (90%) with 5.0 micrograms of platelet-derived growth factor, but the 1.0 microgram group showed similar strength increases, indicating a probable plateau effect in the response. These results indicate that platelet-derived growth factor has promise for healing ligaments but that it must be administered in appropriate doses soon after injury.

Animals↗
PubMed1996

An elastic network model based on the structure of the red blood cell membrane skeleton.

A finite element network model has been developed to predict the macroscopic elastic shear modulus and the area expansion modulus of the red blood cell (RBC) membrane skeleton on the basis of its microstructure. The topological organization of connections between spectrin molecules is represented by the edges of a random Delaunay triangulation, and the elasticity of an individual spectrin molecule is represented by the spring constant, K, for a linear spring element. The model network is subjected to deformations by prescribing nodal displacements on the boundary. The positions of internal nodes are computed by the finite element program. The average response of the network is used to compute the shear modulus (mu) and area expansion modulus (kappa) for the corresponding effective continuum. For networks with a moderate degree of randomness, this model predicts mu/K = 0.45 and kappa/K = 0.90 in small deformations. These results are consistent with previous computational models and experimental estimates of the ratio mu/kappa. This model also predicts that the elastic moduli vary by 20% or more in networks with varying degrees of randomness. In large deformations, mu increases as a cubic function of the extension ratio lambda 1, with mu/K = 0.62 when lambda 1 = 1.5.

Biophysical Phenomena↗
PubMed1996

The nucleosomal array: structure/function relationships.

A nucleosomal array consists of core histone octamer-DNA complexes spaced at approximately 200 bp intervals along a DNA molecule. Nucleosomal arrays are the fundamental building block of chromosomal superstructures, the substrate for transcription, and the first nucleoprotein assembly laid down after DNA replication. The development of homogeneous length-defined nucleosomal arrays has led to a greatly improved understanding of nucleosomal array structural dynamics in the solution state. Under physiological salt conditions, a nucleosomal array is in dynamic equilibrium between folded, self-associated and dissociated conformational states. Folding and self-association are both critically dependent on the core histone tail domains, consistent with an essential functional role for the tail domains in the mediation of chromosomal level DNA compaction in the nucleus. Nucleosomal array folding is repressive in transcription in vitro, but can be overcome by compositional (e.g., tail domain acetylation) and configurational (e.g., histone octamer depletion) changes that are correlated with transcriptional activation in vivo. The mechanism of replication-coupled chromatin assembly also appears to be functionally linked to the dynamic properties of nucleosomal arrays. Although once thought to be both structurally and functionally inert, it is now apparent that the nucleosomal array is a key participant in the biological processes that take place within the chromosomal fibers of eukaryotes.

Animals↗
PubMed1996

Selenium and fertility in animals and man--a review.

To evaluate the information on selenium with relation to fertility in animals and man the available literature was reviewed. Selenium is incorporated in the sperm mitochondria capsule and may thus affect the behavior and function of the spermazoon. Se seems to be essential for normal spermatozoa development in both experimental animals and in livestock and probably also in humans. Regarding selenium and female fertility only sparse information exists. In experimental animals a low selenium level affects fertility in males, but little attention has been devoted to female reproductive performance, and the data are insufficient for conclusion. In livestock numerous investigations have been performed and the effects of selenium supplementation often in combination with other antioxidants have been evaluated, but no valid conclusion can be drawn. In general adequate nutritional supply will secure optimal reproduction in both males and females, while additional supplementation seems to have a negative effect. In humans contradictive information is found. Both low and high sperm selenium concentrations are reported to have a negative influence on the number of spermatozoa and on the motility. The optimal sperm selenium concentration waits to be defined. Some evidence indicates that a metabolic defect in a selenium incorporation into sperm cells may be associated with human infertility. No human data relating selenium to female infertility were found.

Animals↗
PubMed1996

The Inuit diet. Fatty acids and antioxidants, their role in ischemic heart disease, and exposure to organochlorines and heavy metals. An international study.

Traditional food is culturally, economically and nutritionally important for the Greenlandic Inuit people. In the 1970s the preventive effect of marine fat on cardiovascular disease, thrombosis and atherosclerosis was described. The low incidence of ischemic heart disease among Greenlanders has been related to the high intake of marine food. Since 1990 routine autopsies have taken place in two towns in Greenland, Nuuk and Ilulissat. The autopsies represent 26% of the total number of deaths in these two towns. Samples have been collected from 104 autopsies. International cooperative studies have analysed specimens in relation to ischemic heart disease as a benefit related to diet, as well as the level of heavy metals and organochlorine in organs as a risk related to diet. High amounts of mono-unsaturated and Omega-3 poly-unsaturated fatty acid were found in adipose tissue. Liver analyses of selenium have confirmed the expected high intake among Greenlanders. Reduced atherosclerotic lesions were found in the coronary arteries. Blood pressure levels calculated from renovascholopathia of hypertension indicate prevailing levels similar to those in industrialized countries. Some factors in Greenland may be protecting the coronary arteries, thereby of setting the expected effect of hypertension. The level of methyl mercury in organs is generally high. PCB concentrations found in organs of Greenlanders are higher than among other populations. Health and risk effects of the traditional foods need further investigation.

Adipose Tissue↗
PubMed1996

Effects of smoking and marine diet on birthweight in Greenland.

The associations of maternal smoking and blood mercury concentration on birthweight were studied in 1106 liveborn singletons from Greenland with a gestational period of 37+ weeks. After control for population group, smoking was significantly associated with low birthweight while consumption of marine mammals, maternal or cord blood mercury concentration were not. Only in West Greenlanders a week association was found between mercury and low birthweight. The Greenlandic diet of marine mammals has high concentrations of mercury and organochlorines which may reduce birthweight, and it is rich in n-3 fatty acids which have been shown to prolong pregnancy and thereby increase birthweight. In the present study neither previous reports of a negative influence of marine diet on birthweight due to methylmercury or previous reports of a positive influence of marine diet on birthweight due to n-3 fatty acids were supported.

Adult↗
PubMed1995

Core histone tail domains mediate oligonucleosome folding and nucleosomal DNA organization through distinct molecular mechanisms.

Defined oligonucleosome model systems have been used to investigate the molecular mechanisms through which the core histone tail domains modulate chromatin structure. In low salt conditions, the tail domains function at the nucleosome level to facilitate proper organization of nucleosomal DNA, i.e. wrapping of DNA around the histone octamer. Mg2+ ions can substitute for the tail domains to yield a trypsinized oligonucleosome structure that is indistinguishable from that of an intact nucleosomal array in low salt. However, Mg(2+)-dependent formation of highly folded oligonucleosome structures absolutely requires the histone tail domains, and is associated with rearrangement of the tails to a non-nucleosomal location. We conclude that the tail domains mediate oligonucleosome folding and nucleosomal DNA organization through fundamentally different molecular mechanisms.

Animals↗
PubMed1995

Quantitative and qualitative distribution of mercury in organs from arctic sledgedogs: an atomic absorption spectrophotometric and histochemical study of tissue samples from natural long-termed high dietary organic mercury-exposed dogs from Thule, Greenland.

Organs from 10 sledgedogs fed methyl mercury-containing organs and meat from predatory marine animals also eaten by humans in the Thule district of Greenland, were examined histochemically for cellular distribution of mercury, and the organ concentrations of mercury were quantified by atomic absorption spectrometry (total Hg). In selected organs the methyl mercuric level was determined by gaschromatography. The highest concentration of total mercury was found in mesenterial lymph nodes followed by liver and kidneys, which indicates that the lymphatic system might play an important role in the regulating transport of mercury to target organs. The concentrations were age-related, and the results suggest that demethylation takes place in all organs except skeletal muscles, but lowest in CNS. The distribution of mercury at cellular and subcellular levels was studied by the autometallographic technique. The atomic absorption spectrometric and autometallographic results were in good agreement. The brain mean concentration in the oldest group was 438 micrograms/kg, a level much lower than what has been reported to cause effects in the human central nervous system. However, if humans over a period of e.g. 50 years eat Arctic marine meat and accumulate mercury in the same way as dogs, the possibility that this may have health implications cannot be entirely excluded.

Aging↗
PubMed1994

Pyruvate dehydrogenase multienzyme complex. Characterization of assembly intermediates by sedimentation velocity analysis.

The pyruvate dehydrogenase complex is a large, highly organized assembly of several different catalytic and regulatory component enzymes. The structural core of the complex is the E2-X subcomplex, consisting of 60 dihydrolipoamide transacetylase (E2) subunits arranged in a pentagonal dodecahedron; 6 protein X and 2 pyruvate dehydrogenase kinase molecules are tightly associated with this E2 60-mer. The native E2-X subcomplex exhibits a sedimentation coefficient of 32 S. The effects of several chaotropes (guanidinium chloride, potassium thiocyanide, and urea) on the E2-X subcomplex were assessed. Treatment of the E2-X subcomplex with 4 M guanidinium chloride caused a complete loss of enzymatic activity and the dissociation of the subcomplex into monomeric 1.5-3 S species. Removal of the chaotrope by dialysis for 18 h resulted in complete restoration of E2 enzymatic activity and reassembly of a 32 S subcomplex; this reassembled subcomplex contained less protein X than the native subcomplex. Sedimentation velocity analysis of reassembled E2-X subcomplex demonstrated the presence of an 8 S assembly intermediate; this sedimentation coefficient is characteristic of globular proteins of molecular weights similar to that expected for a trimer of E2. Shorter periods of dialysis also gave rise to the 8 S species; the amount of this intermediate decreased with increasing times of dialysis. The 8 S species associated non-cooperatively to yield additional assembly intermediates exhibiting sedimentation coefficients of 10-32 S.

Acetyltransferases↗
PubMed1994

Quantitative analysis of macromolecular conformational changes using agarose gel electrophoresis: application to chromatin folding.

Quantitative analysis of chromatin electrophoretic mobility (mu) in agarose gels provides a measure of three structural parameters: average surface electrical charge density, which is proportional to the gel-free mu (mu 0), effective radius (Re), and particle deformability [Fletcher, T. M., Krishnan, U., Serwer, P., & Hansen, J. C. (1994) Biochemistry 33, 2226-2233]. To determine whether the intramolecular conformational changes associated with salt-dependent chromatin folding influence these electrophoretic parameters, defined oligonucleosomes were reconstituted from monodisperse tandemly repeated 5S DNA and varying amounts of histone octamers. These oligonucleosomes were subjected to both quantitative agarose gel electrophoresis and analytical velocity ultracentrifugation in buffers containing 0-2 mM MgCl2. Ionic conditions that caused a 40% increase in the oligonucleosome sedimentation coefficient (s20,w) also caused both a 30% decrease in Re and a 60% decrease in the magnitude of the mu 0. Furthermore, the Mg(2+)-dependent changes in s20,w, Re, and mu 0 each exhibited the same nonlinear dependence on the degree of nucleosome saturation of the DNA. These data demonstrate that quantitative agarose gel electrophoresis can be used to detect and characterize the process of chromatin folding. In addition, they suggest that this approach can be used for characterization of the conformational dynamics of many other types of macromolecular assemblies, including those systems that are not yet amenable for study by more traditional quantitative biophysical techniques.

Animals↗
PubMed1994

Formation and stability of higher order chromatin structures. Contributions of the histone octamer.

Unique roles have been identified for the histone octamer in the formation and stabilization of higher order chromatin structures. Histone octamers were assembled onto 12 tandem repeats of Lytechinus 5 S rDNA, at either saturating or subsaturating ratios. The extent of oligonucleosome folding and intermolecular association in divalent salts was monitored using analytical and differential sedimentation techniques. Saturated oligonucleosomes (12 nucleosomes/DNA) sedimented at 29 S in very low salt buffer. In 1.0-2.0 mM MgCl2, saturated oligonucleosomes formed a maximally folded 55 S structure whose extent of compaction was equivalent to that of classical higher order 30-nm diameter chromatin structures. These results are in marked contrast to those obtained previously in NaCl, where the maximally folded oligonucleosome species sedimented at only approximately 40 S (Hansen, J. C., Ausio, J., Stanik, V. H., and van Holde, K. E. (1989) Biochemistry 28, 9129-9136). Mg(2+)-dependent formation of the 55 S conformation was inhibited by histone octamer depletion; the maximum sedimentation coefficient observed for rDNA molecules containing 10-11 nucleosomes in 2.0 mM MgCl2 was only 40 S. Above 2.0 mM MgCl2, the equilibrium was progressively shifted toward formation of large associated oligonucleosome species. The implications of these results to the mechanism of chromatin folding and its relationship to the biological activity of the chromatin fiber are discussed.

Animals↗
PubMed1994

A role for histones H2A/H2B in chromatin folding and transcriptional repression.

Histone octamers or histone H3/H4 tetramers were reconstituted onto either closed circular plasmids containing a single Xenopus 5S rRNA gene or a reiterated array of Lytechinus 5S rRNA genes. All "reconstitutes" were found to undergo both Na(+)-dependent and Mg(2+)-dependent compaction. However, in each case, the compaction of nucleosomal templates containing H2A/H2B was much more extensive than compaction of templates containing only H3/H4 tetramers. Inclusion of 5 mM MgCl2 in the transcription buffer increased the level of compaction of nucleosomal templates and led to a marked inhibition of both transcription initiation and elongation by RNA polymerase III. The inhibitory effect of Mg2+ was reduced significantly when DNA templates contained only H3/H4 tetramers, consistent with their lesser extent of Mg(2+)-dependent compaction. Thus, the removal of histones H2A/H2B from nucleosomal arrays enhances gene activity, in part because of decreased levels of chromatin folding.

Animals↗
PubMed1994

Quantitative agarose gel electrophoresis of chromatin: nucleosome-dependent changes in charge, sharp, and deformability at low ionic strength.

The surface electrical charge density and the deformability of nucleosomal arrays have been characterized by quantitative agarose gel electrophoresis. Monodisperse linear DNA (2.5-3.3 kbp) was reconstituted with histone octamers into either saturated (approximately 1 nucleosome/200-bp DNA) or subsaturated (< 1 nucleosome/200-bp DNA) nucleosomal arrays. The electrophoretic mobility (mu) of both nucleosome-free DNA and nucleosomal arrays was determined at low ionic strength in 0.2-3.0% agarose gels. A semilogarithmic plot of mu vs gel concentration was linear for DNA and convex for saturated nucleosomal arrays. By extrapolating the mu to 0% agarose, the magnitude of the gel-free mu of saturated nucleosomal arrays was found to be approximately 20% lower than that of nucleosome-free DNA molecules. This difference is explained by the net neutralization of approximately 85 DNA negative charges by each histone octamer. By using an internal standard to measure the effective pore size (Pe) of the agarose gel, the effective radius (R) of DNA and nucleosomal arrays was determined at each agarose concentration. In the more dilute gels (Pe > or = 400 nm), the differences between the effective R values of DNA, subsaturated nucleosomal arrays, and saturated nucleosomal arrays are consistent with the differences in their hydrodynamic shapes as measured by analytical velocity centrifugation. However, as Pe decreases, the effective R of both nucleosome-free DNA and subsaturated nucleosomal arrays decreases significantly. This is in contrast to the effective R of saturated nucleosomal arrays, which remains constant at all Pe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Fatty acids and antioxidants in the Inuit diet. Their role in ischemic heart disease (IHD) and possible interactions with other dietary factors. A review.

The recent literature on the role of fatty acids and antioxidants as protective factors in ischemic heart disease (IHD) has been reviewed. Serum cholesterol, especially LDL-cholesterol, is regarded as an index of risk for IHD. Epidemiological studies have connected a high dietary intake of n-3 fatty acids with a low occurrence of IHD. It is believed that this effect is brought about by a modification of the eicosanoid synthesis and a lowering of the cholesterol level. Intervention studies have not demonstrated that n-3 acids can lower the level whereas monounsaturated fatty acids (MUFAs) have been shown to have such an effect although they were previously believed to be neutral. The epidemiological observations probably reflect the combined effect of both n-3 polyunsaturated fatty acids (PUFAs) and MUFAs. Recently, oxidized LDL has been suggested to be involved in the earliest lesion of atherogenesis. This hypothesis suggest that the antioxidant balance is an important factor for IHD. As the traditional Greenlandic diet is rich in n-3 PUFAs, MUFAs and antioxidants (selenium), epidemiological studies in Greenland could shed important light on the role of individual dietary components and their interactions.

Antioxidants↗
PubMed1993

Assembly and structural properties of subsaturated chromatin arrays.

Nucleosomes have been reconstituted onto dodecameric repeats of a 208-base pair nucleosome positioning sequence at various subsaturating molar ratios of histone octamer to DNA repeat (r). These reconstitutes have been characterized with respect to lattice site occupancy distributions, nucleosome positioning, chromatin folding, and histone octamer dissociation. Reconstitution at 0.3 < or = r < or = 0.9 produces subsaturated chromatin templates with distinct compositional limits, n +/- 2 nucleosomes, where n is the average number of nucleosomes present on the template at that r value. Nucleosomes on subsaturated arrays occupy the same set of specific positions within the repeat unit as they do on saturated templates, with only very slight differences in the relative frequency of occupation of the various positions. The nucleosomes on very subsaturated templates, i.e. r < or = 0.5, are generally spread out. However, some nucleosome clustering is observed on these very subsaturated templates. These results indicate that assembly of nucleosomes onto this DNA lattice is not a strongly cooperative process. In 200 mM NaCl, subsaturated reconstitutes exhibit reduced levels of folding and histone octamer dissociation compared with saturated arrays. These results provide a framework for understanding the structural features of regions of chromatin partially depleted of nucleosomes.

Animals↗