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L H Jensen

Publications and source records attributed to L H Jensen.

At least 19 recordsLinked to original sources
PubMed1998

In vivo and in vitro evaluation of AMPA receptor antagonists in rat hippocampal neurones and cultured mouse cortical neurones.

The effects of four glutamate receptor antagonists on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-responses were evaluated using both in vitro and in vivo electrophysiological techniques: whole cell patch-clamp recordings from cultured mouse cortical neurones and microiontophoresis in the rat hippocampus. The compounds tested were NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8-methyl-endioxyl-5H-2,3-benzodiaze pine), PNQX (pyrido[3, 4-f]quinoxaline-2,3-dione, 1,4,7,8,9,10-hexahydro-9-methyl-6-nitro-, methanesulfonate), NS377 (7-ethyl-5-phenyl-1,6,7,8-tetrahydro-1,7-diaza-as-indacene-2 ,3-dione), and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenz(a,d)cycloheptene-5,10-imine hydrogen maleate). In vitro, the IC50 values (in microM) for inhibition of AMPA-evoked inward currents were approximately 0.4 for NBQX, approximately 7.5 for GYKI 52466, approximately 1 for PNQX and approximately 15 for NS377. PNQX and NS377 also inhibited NMDA-induced currents with IC50 values at approximately 5 and approximately 18 microM, respectively, while NBQX at 60 microM and GYKI 52466 at 100 microM had only weak effects. The ED50 values in micromol/kg i.v. for inhibition of AMPA-evoked hippocampal neuronal spike activity in vivo were approximately 32 for NBQX, approximately 19 for GYKI 52466, approximately 17 for PNQX and approximately 11 for NS377 with efficacy values (maximal inhibition) between 71% and 81%. The ED50 values (in [Lmol/kg i.v.) and efficacy values for inhibition of NMDA-evoked hippocampal neuronal spike activity were approximately 28 with an efficacy of 61% for NBQX, approximately 16 with 35% for PNQX and approximately 6 with 61% for NS377. GYKI 52466 did not significantly affect NMDA responses, whereas MK-801 showed NMDA specificity in vivo.

Action Potentials↗
PubMed1998

Chinese hamster ovary cells resistant to the topoisomerase II catalytic inhibitor ICRF-159: a Tyr49Phe mutation confers high-level resistance to bisdioxopiperazines.

Anticancer drugs targeted to the nuclear enzyme DNA topoisomerase II are classified as poisons that lead to DNA breaks or catalytic inhibitors that appear to completely block enzyme activity. To examine the effects of the bisdioxopiperazine class of catalytic inhibitors to topoisomerase II, we investigated a Chinese hamster ovary (CHO) subline selected for resistance to ICRF-159 (CHO/159-1). Topoisomerase IIalpha content in CHO/159-1 cells was reduced by 40-50%, compared to wild-type CHO cells, whereas the beta isoform was increased by 10-20% in CHO/159-1 cells. However, the catalytic activity of topoisomerase II in nuclear extracts from CHO/159-1 cells was unchanged, as was its inhibition by the topoisomerase II poison etoposide (VP-16). No inhibition of topoisomerase II catalytic activity by ICRF-187 was seen in CHO/159-1 cells up to 500 microM, whereas inhibition was evident at 50 microM in wild-type CHO cells. VP-16-mediated DNA single-strand breaks and cytotoxicity were similar in the two sublines. ICRF-187 could abrogate these VP-16 effects in the wild-type line but had no effect in CHO/159-1 cells. Western blots of topoisomerase IIalpha after incubation of CHO cells with ICRF-187 demonstrated a marked band depletion, whereas this effect was completely lacking in CHO/159-1 cells, and an equal effect of VP-16 was observed in both lines. These data imply that the CHO/159-1 topoisomerase IIalpha lacks sensitivity to bisdioxopiperazines and that the mechanism of resistance in this cell line does not confer cross-resistance to topoisomerase II poisons, suggesting that mutations conferring resistance to bisdioxopiperazines can occur at sites distinct from those responsible for resistance to complex stabilizing agents. Accordingly, CHO/159-1 cDNA showed two heterozygous mutations in the proximal NH2-terminal part of topoisomerase IIalpha (Tyr49Phe and delta 309Gln-Gln-Ile-Ser-Phe313), which is in contrast to those induced by topoisomerase II poisons, which cluster further downstream. Site-directed mutagenesis and transformation of the homologous Tyr50Phe coding mutation in human topoisomerase IIalpha in a temperature-conditional yeast system demonstrated a high-level resistance to ICRF-193, compared to cells expressing wild-type cDNA, but none toward the poisons VP-16 or amsacrine, thus confirming that the Tyr50Phe mutation confers specific resistance to bisdioxopiperazines. Thus, these results indicate that the region of the protein involved in ATP-binding also plays a critical role in sensitivity to bisdioxopiperazines, a result consistent with the known requirement for the formation of an ATP-bound closed clamp for bisdioxopiperazine activity. These results may enable a more precise understanding of the interaction of topoisomerase II-directed drugs with their target enzyme.

Amino Acid Sequence↗
PubMed1996

Cognitive theory applied to the treatment of delusions of schizophrenia.

This article reviews theory regarding cognitive interventions in schizophrenia, focusing particularly on the treatment of delusions. The cognitive theory of psychopathology is first introduced and the specific goals of cognitive therapy are then presented. A range of philosophical and etiologic perspectives on the nature of delusions are explored, including the cognitive perspective. Specific stages and techniques of therapy are discussed with theoretical underpinnings and suggestions for incorporation in advanced practice psychiatric nursing.

Cognitive Behavioral Therapy↗
PubMed1995

Pharmacological profile and anti-ischemic properties of the Ca(2+)-channel blocker NS-638.

Included in the sequence of events leading to neuronal death in ischemic tissue following stroke is an excessive and toxic rise in the intracellular Ca(2+)-concentration, predominantly due to an influx of Ca2+ through nonselective cation-channels as well as Ca(2+)-channels. In the present study we have characterized the pharmacological profile and anti-ischemic effects of 2-amino-1-(4-chlorobenzyl)-5-trifluoromethylbenzimidazole (NS-638), a small nonpeptide molecule with Ca(2+)-channel blocking properties. NS-638 dose dependently inhibited K(+)-stimulated [45Ca2+]-uptake in chick cortical synaptosomes and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)-stimulated [3H]GABA-release from cultured cortical neurons with IC50 values of 2.3 and 4.3 microM, respectively. K(+)-stimulated intracellular Ca(2+)-elevation in cultured cerebellar granule cells was equipotently blocked with an IC50 value of 3.4 microM. At this concentration no effect on Ca(2+)-induced contractions in K(+)-depolarized guinea pig taenia coli was observed. The effect of NS-638 on neuronal Ca(2+)-channels was evaluated using whole cell patch clamp techniques. The compound reversibly blocked N- and L-type Ca(2+)-channels in cultured chick dorsal root ganglion cells in the concentration range of 1-30 microM. In the mouse middle cerebral artery occlusion (MCAO) model, NS-638 administered i.p. (50 mg kg-1) at 1 h and 6 h post-ischemia, and once a day for the next two days, resulted in a 48% reduction in total infarct volume. The compound did not show protection against ischemic neuronal damage in the gerbil model of bilateral carotid artery occlusion (BCAO). This data suggests, that neuronal Ca(2+)-channel blockers may have potential in ameliorating the pathological damage after focal ischemia.

Animals↗
PubMed1994

[Patterns of tuberculosis manifestation in the county of Roskilde].

The epidemiological and clinical features of all adult tuberculosis (tbc) cases in a Danish county over a 12 year period (82 cases) are presented. Most patients with pulmonary disease have thorax X-ray pictures showing pathological changes. Of the patients who only have extrapulmonary disease, 88% have normal X-ray examinations of the lungs. The patients can be divided into two groups: Danes and foreigners. The Danish patients are older, 81% are over the age of forty. They mostly have pulmonary disease (85%). They often have one or several concomitant diseases. The foreigners are younger, 90% are below the age of forty. They frequently have extrapulmonary disease (35%). They seldom have concomitant diseases.

Adolescent↗
PubMed1994

Relation of spatial learning of rats in the Morris water maze task to the number of viable CA1 neurons following four-vessel occlusion.

Male Wistar rats were tested in the Morris water maze task 1 week after 6, 9, or 12 min of transient global ischemia. The 9-min and 12-min ischemia groups were significantly impaired in the acquisition and the reversal experiment. A systematic counting of CA1 neurons in the whole hippocampal formation revealed a unilateral number of CA1 neurons of 286,000 in the sham group, of which 2/3 were located in the dorsal hippocampus. The ischemia groups showed a significant decline in the number of dorsal CA1 neurons, whereas only the 12-min ischemia group showed a significant but minor decline (10%-15%) in the number of ventral CA1 neurons. A correlation analysis showed that the escape distance declined with increasing number of viable CA1 neurons, but poor correlation coefficients were obtained. Thus, some of the ischemic rats with even very few viable CA1 neurons in the dorsal hippocampus were capable of performing this spatial learning task at sham-group level.

Animals↗
PubMed1994

Does neuronal damage of CA1 relate to spatial memory performance of rats subjected to transient forebrain ischemia?

The effect of ischemia-induced hippocampal neuronal damage on acquisition and performance in the Morris water maze task was investigated in male Wistar rats, subjected to 8 min of transient forebrain ischemia, induced by the 4-vessel occlusion (4-VO) method. After a morphological scoring of the neuronal damage within the CA1, CA2, and CA3 subfields of the anterior-dorsal part of hippocampus we found that rats with a total neuronal cell loss of the anterior-dorsal CA1 region showed memory performance impairments in the acquisition trials, in a probe trial, and in a reversal experiment. However, rats with only partial damage to the CA1 region did not exhibit significant impairments during the acquisition trials of the water maze test or in the probe trial and the reversal experiment. In conclusion, these results suggest that it is possible to relate the histological damage score of CA1 in the anterior-dorsal hippocampus to impaired memory performance in the present water maze setup.

Animals↗
PubMed1993

Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex.

We have examined the effect of cortical spreading depression (SD) and anoxic depolarization (AD) on the interstitial concentration changes of amino acids (AA) in the neocortex of anesthetized rats using microdialysis and HPLC. Accompanying SD alanine increased to 126 +/- 11%, arginine to 116 +/- 3%, aspartate to 160 +/- 17%, glutamate to 163 +/- 9%, glycine to 158 +/- 21%, serine to 125 +/- 9%, and taurine to 172 +/- 15% (mean +/- 1 S.E.M.). The increases lasted for about 1 min. Histidine decreased to 74% +/- 4% at 1 min following SD, and returned to normal 4 min later. Cardiac arrest triggered AD after approximately 2 min, immediately followed by changes of interstitial AAs. At 5 min after AD alanine had increased to 183 +/- 13%, aspartate to 3,458 +/- 656%, GABA to 338 +/- 35%, glutamate to 1,696 +/- 546%, glycine to 297 +/- 37%, serine to 153 +/- 12%, and taurine to 1721 +/- 98% as compared to control values (mean +/- 1 S.E.M.). Histidine decreased to 78 +/- 2% at 3 min following AD while arginine exhibited insignificant variations around the baseline. The increase of glutamate during SD is consistent with activation of NMDA-receptors as an essential requirement for this reaction. The increase of AAs may also contribute to the sequence of events leading to AD, though the exact mechanism remains unknown. SD is an important pathophysiological mechanism of the ischemic penumbra associated with focal cerebral ischemia, while AD reflects the electrophysiological status of the infarct core.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Time- and temperature-dependent forebrain ischemic damage in Mongolian gerbils.

The influence of transient bilateral carotid artery occlusion time, core body temperature regulation and post-operative survival time was examined on delayed neuronal death in the hippocampal subregions of Mongolian gerbils. A simple and rapid histologically based scoring system was used. A carotid artery occlusion time of 5 min with stabile core body temperature at 37.5-38.0 degrees C and a post-operative survival time of 4 days was sufficient to induce a reproducible and almost total neuronal damage in the hippocampal subfields. Furthermore, the use of gerbils with ages varying from 50 to 100 days did not markedly influence the development of the neuronal damage although the variation in the severity of the damage seemed to decrease with age. The addition of a drop of room tempered (21-22 degrees C) isotonic water, to avoid adherence between the clips and the carotid artery, reduced neuronal damage in some animals.

Animals↗
PubMed1992

The structure of water in protein crystals.

Protein crystals grown from aqueous media invariably contain substantial amounts of the crystallizing solution, and the structure of the protein molecules and surrounding solvent can be determined from X-ray diffraction data. Electron density maps of crystalline proteins based on such data show networks of water peaks in the solvent space within approximately 6A of the protein surface. In general, the peaks are highest for water molecules within hydrogen bonding distance of acceptor or donor atoms on the protein. With increasing distance from the protein, the water peaks decrease in height, and beyond approximately 6A they merge into the structureless solvent continuum, typical of most crystalline proteins. A few water sites are often found within the protein molecule. These water molecules appear to be trapped within the protein and presumably are more tightly bound than water external to the protein.

Crystallization↗
PubMed1991

Refined crystal structure of ferredoxin II from Desulfovibrio gigas at 1.7 A.

The crystal structure of ferredoxin II from Desulfovibrio gigas has been determined using phasing from anomalous scattering data at a resolution of 1.7 A and refined to an R-factor of 0.157. The molecule has an overall chain fold similar to that of the other bacterial ferredoxins of known structure. The molecule contains a single 3Fe-4S cluster with geometry indistinguishable from the 4Fe-4S clusters, and a disulfide bond near the site corresponding to the position of the second cluster of two-cluster ferredoxins. The cluster is bound by cysteine residues 8, 14 and 50. The side-chain of cysteine 11 extends away from the cluster, but could rotate to become the fourth cysteine ligand in the four-iron form of the molecule given a local adjustment of the polypeptide chain. This residue is modified, however, by what appears to be a methanethiol group. There are a total of eight NH . . . S bonds to the inorganic and cysteine sulfur atoms of the Fe-S cluster. There is an additional residue found that is not reported for the chemical sequence: according to the electron density a valine residue should be inserted after residue 55.

Amino Acid Sequence↗
PubMed1991

Structure of rubredoxin from Desulfovibrio vulgaris at 1.5 A resolution.

The X-ray model of rubredoxin from Desulfovibrio vulgaris has been refined against 1.5 A X-ray diffraction data collected on a diffractometer. The final model comprises 395 non-hydrogen protein atoms, and 180 solvent O atoms. The final R-value for the model with calculated H atom positions included as fixed contributions is 0.098 over all reflections greater than 2 sigma I from infinity to 1.5 A. The error in co-ordinates is estimated to be 0.08 A. The solvent model was twice redetermined during the later stages of refinement and was instrumental in its success. One sequence error has been detected and corrected (Thr21----Asp). The iron-sulfur site bond angles are distorted from true tetrahedral symmetry, as found in other rubredoxin structures. A significant deviation from tetrahedral angles is seen at C alpha atoms 9, 10, 42 and 43, interior angles of the loops binding the iron atom. The planes of two aromatic groups, Tyr4 and Trp37, are nearly parallel to, and lie under, an extended system of atoms that includes the peptide bonds preceding the first cysteine residue of each cysteine loop as well as the cysteine side-chain, the iron, and the cysteine side-chain of the opposite loop, forming a previously unrecognized extended system that may function in electron transfer.

Amino Acid Sequence↗
PubMed1990

Dopamine release in the nucleus caudatus and in the nucleus accumbens is under glutamatergic control through non-NMDA receptors: a study in freely-moving rats.

Perfusion with quisqualate (5 x 10(-6) M) and kainate (5 x 10(-7) M), selective agonists of glutamate receptors, enhanced the release of dopamine in both caudate and accumbens nuclei of freely-moving rats, measured by the transcerebral microdialysis technique. In contrast, N-methyl-D-aspartate (NMDA) did not affect dopamine release, except at very high concentrations (10(-2) M). The quisqualate-kainate antagonist, FG 9041 (DNQX), antagonized the elevation of dopamine release induced by quisqualate and, furthermore, reduced that of kainate. CPP, a selective NMDA antagonist, did not counteract the quisqualate- or kainate-induced stimulation of dopamine release. The enhancement of dopamine release after quisqualate and kainate was accompanied by behavioural stimulation characterized by grooming, rearing, hypermotility with sniffing and confined sniffing. This behavioural syndrome could be blocked by haloperidol. Conversely, perfusion with NMDA did not activate behaviour even at high concentrations. These results indicate that the dopaminergic system, within the caudate and the accumbens nuclei, is under glutamatergic control through kainate and quisqualate receptors, while the NMDA receptors do not appear to be involved.

Animals↗
PubMed1990

Solvent model for protein crystals: on occupancy parameters for discrete solvent sites and the solvent continuum.

On the basis of test calculations, Kundrot & Richards [Acta Cryst. (1987), B43, 544-547] suggest that for models of protein crystal structures based on limited-resolution X-ray data, it is not appropriate to vary both the occupany (Q) and thermal (B) parameters for the solvent molecules during refinement. There are compelling reasons, however, to adjust both parameters. If the data are sufficiently extensive to include a B parameter for each solvent site, then an adjustable Q parameter should also be included if the model is to represent physical reality. To fix Q at some arbitrary value as suggested, means that differences in occupancy will be absorbed in the 'thermal' parameters, leading to the errors corresponding to the electron density plots of Kundrot & Richards. Although the errors appear to be relatively small, they will be accentuated in Fourier maps of complex structures based on real data, causing error peaks, both positive and negative, that may greatly exceed the random errors. The current practice of using the scattering factor of the O atom, fO, for the water molecule neglects the scattering from the H atoms. A modified scattering factor based on fO- would approximate the scattering from water molecules better. Finally, the solvent continuum should be included in the model, and the low-order data included in calculating the Fourier maps from which the Q parameters are estimated.

Chemical Phenomena↗
PubMed1990

Refinement of triclinic lysozyme: I. Fourier and least-squares methods.

X-ray diffraction data to 1.5 A resolution have been collected for triclinic crystals of hen egg white lysozyme. The triclinic model was derived from the tetragonal one by the rotation function and refined initially by Fo-Fc and differential difference syntheses against 2 A resolution data. Refinement was continued by differential difference cycles against the 1.5 A data until R was reduced to 0.220. Although the initial refinement was rapid, it was subsequently a matter of attrition, leading to a complete recheck of the data and the discovery of systematic error which affected primarily the high-resolution data. Refinement was continued against the corrected 2 A data by block-diagonal least squares. After five cycles the refinement was terminated at R = 0.254 because of the imminent availability of a preferred refinement program. Problems with the protein model, the solvent, and the interaction of the scale and thermal parameters are discussed. The experiences gained in this study are summarized.

Fourier Analysis↗
PubMed1990

Refinement of triclinic lysozyme: II. The method of stereochemically restrained least squares.

Refinement of triclinic lysozyme by restrained least squares against the 2 A resolution X-ray data is described, beginning with the model from cycle 17 of the preceding paper [Hodsdon, Brown, Sieker & Jensen (1990). Acta Cryst. B46, 54-62]. After 20 refinement cycles, R stood at 0.172. Nevertheless, serious errors involving both main-chain and side-chain atoms still remained, requiring numerous model rebuilding sessions interleaved with refinement cycles. After 63 cycles R = 0.124 for the model which includes all protein atoms, 249 water oxygen sites and five nitrate ions. Although the overall B is relatively low, 10.5 A2, B's for atoms in the region of residues 101-103, toward the termini of some of the longer side chains, and in the region of the C terminus of the main chain exceed 20 A2, indicating relatively high atomic mobilities, disorder, or remaining errors in the model.

Computer Simulation↗
PubMed1990

The structure of rubredoxin from Desulfovibrio desulfuricans strain 27774 at 1.5 A resolution.

The structure of a small rubredoxin from the bacterium Desulfovibrio desulfuricans has been determined and refined at 1.5 A resolution. The hairpin loop containing seven residues in other rubredoxins is missing in this 45 residue molecule, and once that fact was determined by amino acid sequencing studies, refinement progressed smoothly to an R value of 0.093 for all reflections from 5 to 1.5 A resolution. Nearly all of the water molecules in the well-ordered triclinic unit cell have been added to the crystallographic model. As in the other refined rubredoxin models, the Fe-S4 complex is slightly distorted from ideal tetrahedral coordination.

Amino Acid Sequence↗