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Biomedical subjects

E Nielsen

Publications and source records attributed to E Nielsen.

At least 19 recordsLinked to original sources

Observation of three-dimensional long-range order in small ion coulomb crystals in an rf trap.

Three-dimensional long-range ordered structures in smaller and near-spherically symmetric Coulomb crystals of (40)Ca(+) ions confined in a linear rf Paul trap have been observed when the number of ions exceeds approximately 1,000 ions. This result is unexpected from ground state molecular dynamics (MD) simulations, but found to be in agreement with MD simulations of metastable ion configurations. Previously, three-dimensional long-range ordered structures have only been reported in Penning traps in systems of approximately 50,000 ions or more.

Journal Article↗

RNA targeting using peptide nucleic acid.

The efforts towards peptide nucleic acid (PNA) drug discovery using cellular RNAs as molecular targets is briefly reviewed, with special emphasis on recent developments. Special attention is given to cellular delivery in vivo bioavailability and the possibilities of using PNA oligomers to (re)direct alternative splicing of pre-messenger (m)RNA.

Animals↗

Radar soundings of the ionosphere of Mars.

We report the first radar soundings of the ionosphere of Mars with the MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) instrument on board the orbiting Mars Express spacecraft. Several types of ionospheric echoes are observed, ranging from vertical echoes caused by specular reflection from the horizontally stratified ionosphere to a wide variety of oblique and diffuse echoes. The oblique echoes are believed to arise mainly from ionospheric structures associated with the complex crustal magnetic fields of Mars. Echoes at the electron plasma frequency and the cyclotron period also provide measurements of the local electron density and magnetic field strength.

Journal Article↗

MRI in chronic spinal cord injury patients with and without central pain.

BACKGROUND: Central pain following spinal cord injury (SCI) is common and thought to be related to lesion of the spinothalamic pathways. OBJECTIVE: To examine additional mechanisms of SCI pain. METHODS: Twenty-three SCI patients with traumatic lesions above T10 (14 with central neuropathic pain and 9 without pain) underwent MRI examination. The authors quantitatively assessed extent of cord lesion on axial T2-weighted images as percentage of 1) gray matter, 2) dorsolateral, 3) anterolateral, and 4) dorsolateral columns based on standardized drawings made by a neuroradiologist blinded to patient history. RESULTS: At the level of maximal cord injury, 21 patients had lesions involving the entire cord on axial images except for a small border of lower signal intensity, whereas 2 patients had central lesions. Rostral to the main injury, the first image with an incomplete lesion showed significantly more involvement of gray matter in pain than in pain-free patients. CONCLUSION: Consistent with animal models of SCI, spinothalamic tract lesion together with neuronal hyperexcitability due to lesion of inhibitory interneurons at the rostral end of injury are hypothesized to lead to central pain.

Adult↗

Phenotypic, genetic and molecular characterization of a maize low phytic acid mutant (lpa241).

Phytic acid, myo-inositol 1,2,3,4,5,6-hexakisphosphate, is the major storage compound of phosphorous (P) in plants, predominantly accumulating in seeds (up to 4-5% of dry weight) and pollen. In cereals, phytic acid is deposited in embryo and aleurone grain tissues as a mixed "phytate" salt of potassium and magnesium, although phytates contain other mineral cations such as iron and zinc. During germination, phytates are broken down by the action of phytases, releasing their P, minerals and myo-inositol which become available to the growing seedling. Phytic acid represents an anti-nutritional factor for animals, and isolation of maize low phytic acid ( lpa) mutants provides a novel approach to study its biochemical pathway and to tackle the nutritional problems associated with it. Following chemical mutagenesis of pollen, we have isolated a viable recessive mutant named lpa 241 showing about 90% reduction of phytic acid and about a tenfold increase in seed-free phosphate content. Although germination rate was decreased by about 30% compared to wild-type, developement of mutant plants was apparentely unaffected. The results of the genetic, biochemical and molecular characterization experiments carried out by SSR mapping, MDD-HPLC and RT-PCR are consistent with a mutation affecting the MIPS1S gene, coding for the first enzyme of the phytic acid biosynthetic pathway.

Animals↗

Narcotics at street level in Denmark. A prospective investigation from 1995 to 2000.

This article describes an investigation of illicit drugs at street level in six selected police districts in different regions of Denmark. The investigation was carried out during a 6-year period from 1995 to 2000. During the period, a total of 1244 samples were examined, as about 200 samples were seized each year. A total of 94% of the seized samples were familiar drugs: heroin base, heroin hydrochloride, cocaine hydrochloride and amphetamine sulphate. Only 2% of the samples contained designer drugs. From having constituted 53% of the samples in 1995, the frequency of heroin base fell during the period to 27% of the samples in 2000. The frequency of heroin hydrochloride was unchanged. In the same period, the frequency of cocaine hydrochloride increased from 10% of the samples in 1995 to about 25% of the samples in 2000. Apart from a few exceptions, cocaine had the same extension in all regions of Denmark after 1996. Amphetamine was more frequent in the west of Denmark, while heroin hydrochloride was more frequent in central Denmark. The purity of heroin base was lower in the period 1997-1999 than in the other years. During the entire period, the purity of cocaine hydrochloride and amphetamine sulphate fell, while the purity of heroin hydrochloride was unchanged. No significant differences between the various regions of Denmark were detected during the period in the purity of heroin hydrochloride, heroin base, cocaine hydrochloride or amphetamine sulphate. MDMA was the most frequent designer drug, but other types of designer drugs such as MDA and MDE and the less common PMA, PMMA and MBDB were also found.

Amphetamine↗

Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain.

Rab5 regulates endocytic membrane traffic by specifically recruiting cytosolic effector proteins to their site of action on early endosomal membranes. We have characterized a new Rab5 effector complex involved in endosomal fusion events. This complex includes a novel protein, Rabenosyn-5, which, like the previously characterized Rab5 effector early endosome antigen 1 (EEA1), contains an FYVE finger domain and is recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. Rabenosyn-5 is complexed to the Sec1-like protein hVPS45. hVPS45 does not interact directly with Rab5, therefore Rabenosyn-5 serves as a molecular link between hVPS45 and the Rab5 GTPase. This property suggests that Rabenosyn-5 is a closer mammalian functional homologue of yeast Vac1p than EEA1. Furthermore, although both EEA1 and Rabenosyn-5 are required for early endosomal fusion, only overexpression of Rabenosyn-5 inhibits cathepsin D processing, suggesting that the two proteins play distinct roles in endosomal trafficking. We propose that Rab5-dependent formation of membrane domains enriched in phosphatidylinositol-3-phosphate has evolved as a mechanism for the recruitment of multiple effector proteins to mammalian early endosomes, and that these domains are multifunctional, depending on the differing activities of the effector proteins recruited.

Amino Acid Motifs↗

[Hantavirus disease during pregnancy].

Hantavirus infection is known to occur in mice and rats without symptoms. In contrast, an infection with Hantavirus in humans gives influenzalike symptoms and acute renal failure. The treatment is symptomatic, but treatment with dialysis can be necessary for a while. A case of Hantavirus infection in Denmark in a 30 week pregnant woman is reported.

Acute Kidney Injury↗

Direct analysis of artemisinin in plasma and saliva using coupled-column high-performance liquid chromatography with a restricted-access material pre-column.

A previously established HPLC system with post-column derivatization for the analysis of artemisinin was coupled to an ADS (alkyl-diol silica) pre-column, allowing direct and repetitive injection of protein-rich fluids such as plasma. The limit of quantitation for 100 microl of plasma was 10 ng/ml (CV=10.5%) while concentrations down to 2 ng/ml could be quantified for 1.00 ml saliva samples (CV=11.1%). The system was linear in the tested range of 10-2000 ng/ml for plasma and 2-240 ng/ml for saliva samples, respectively. This paper introduces coupled column HPLC as a simplified method for the routine analysis of artemisinin in biological fluids.

Antimalarials↗

Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11.

Two endosome populations involved in recycling of membranes and receptors to the plasma membrane have been described, the early and the recycling endosome. However, this distinction is mainly based on the flow of cargo molecules and the spatial distribution of these membranes within the cell. To get insights into the membrane organization of the recycling pathway, we have studied Rab4, Rab5, and Rab11, three regulatory components of the transport machinery. Following transferrin as cargo molecule and GFP-tagged Rab proteins we could show that cargo moves through distinct domains on endosomes. These domains are occupied by different Rab proteins, revealing compartmentalization within the same continuous membrane. Endosomes are comprised of multiple combinations of Rab4, Rab5, and Rab11 domains that are dynamic but do not significantly intermix over time. Three major populations were observed: one that contains only Rab5, a second with Rab4 and Rab5, and a third containing Rab4 and Rab11. These membrane domains display differential pharmacological sensitivity, reflecting their biochemical and functional diversity. We propose that endosomes are organized as a mosaic of different Rab domains created through the recruitment of specific effector proteins, which cooperatively act to generate a restricted environment on the membrane.

Androstadienes↗

Intracranial sarcoma in a patient with neurofibromatosis type 2 treated with gamma knife radiosurgery for vestibular schwannoma.

OBJECTIVE: To discuss the possible relationship between stereotactic radiation therapy and the development of a meningosarcoma. STUDY DESIGN: Retrospective case review. PATIENT: A 19-year-old woman with bilateral vestibular schwannomas (neurofibromatosis type 2). One large tumor was removed totally by the translabyrinthine approach; the other smaller tumor was treated with stereotactic radiation (SRT). Six years after SRT, a malignant tumor (meningosarcoma) developed at the exact site of radiation. The patient subsequently died of this tumor. OUTCOME MEASURE: On the basis of literature surveys, the possibility and risk of postirradiation neoplasia after SRT is discussed. Furthermore, the possible causal association between SRT and the development of the meningosarcoma in this case is evaluated. CONCLUSION: On the basis of statistical considerations, the development of the reported mesenchymal sarcoma was most likely caused by the stereotactic radiation therapy.

Adult↗

Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability.

The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, genistein and equol was investigated in immature female mice. Genistein and equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17-20, 100 mg/kg body weight], was found to significantly increase uterine weights and the overall uterine concentration of estrogen receptor alpha (ERalpha). In kaempferol- and equol-exposed mice the cytosolic ERalpha concentration was significantly increased as compared to the solvent control, which is speculated to result in an increased sensitivity of the uterus to subsequently encountered estrogens. Oral administration of equol, genistein, biochanin A and daidzein to 6-week-old female mice revealed a great variation in their systemic bioavailability. The urinary recovery of equol was thus over 90% of a single gavage administered dose, whereas the urinary recoveries of biochanin A, genistein and daidzein were 16, 11 and 3%, respectively. Most of the metabolites were either hydroxylated or dehydrogenated forms of the parent compounds. The in vitro estrogenic potency of some of the metabolites was greater than that of the parent compounds, whereas others were of similar or lower potency. Bioavailability, metabolism, the ability to alter ERalpha distribution in the uterus and the estrogenic potential of parent compound and metabolites may thus contribute to the differences in in vivo estrogenicity of dietary flavonoids.

Animals↗

Rab5 regulates motility of early endosomes on microtubules.

The small GTPase Rab5 regulates membrane docking and fusion in the early endocytic pathway. Here we reveal a new role for Rab5 in the regulation of endosome interactions with the microtubule network. Using Rab5 fused to green fluorescent protein we show that Rab5-positive endosomes move on microtubules in vivo. In vitro, Rab5 stimulates both association of early endosomes with microtubules and early-endosome motility towards the minus ends of microtubules. Moreover, similarly to endosome membrane docking and fusion, Rab5-dependent endosome movement depends on the phosphatidylinositol-3-OH kinase hVPS34. Thus, Rab5 functionally links regulation of membrane transport, motility and intracellular distribution of early endosomes.

Biological Transport↗

One-on-one peer support and quality of life for breast cancer patients.

The Canadian Cancer Society's Reach to Recovery program provides one-on-one support for breast cancer patients that is delivered by breast cancer survivors. Professionally-led social support programs have generally been found to influence positively the quality of life of cancer patients. However, there is a lack of evidence on the benefits of one-on-one peer support programs. An evaluation of the Reach to Recovery program was completed in 1995 to determine if cancer patients who received the program were satisfied with the program and to determine if participation in Reach to Recovery affected the quality of life of program participants compared to patients who did not receive the program. We found that Reach to Recovery program participants were generally satisfied with the program they received and that the program has incremental benefits to the quality of life of patients with breast cancer. Peer-led, volunteer breast cancer support programs can be effective in enhancing the quality of life of breast cancer patients.

Adult↗

Effects of sevoflurane on intracranial pressure, cerebral blood flow and cerebral metabolism. A dose-response study in patients subjected to craniotomy for cerebral tumours.

BACKGROUND: Studies concerning the cerebrovascular effects of sevoflurane in patients with space-occupying lesions are few. This study was carried out as a dose-response study comparing the effects of increasing sevoflurane concentration (1.5% (0.7 MAC) to 2.5% (1.3 MAC)) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR), metabolic rate of oxygen (CMRO2) and CO2-reactivity in patients subjected to craniotomy for supratentorial brain tumours. METHODS: Anaesthesia was induced with propofol/fentanyl/atracurium and maintained with 1.5% sevoflurane in air/oxygen at normocapnia. Blood pressure was maintained constant by ephedrine. In group 1 (n = 10), the patients received continuously 1.5% sevoflurane. Subdural ICP, CBF and CMRO2 were measured twice at 30-min intervals. In group 2 (n = 10), sevoflurane concentration was increased from 1.5% to 2.5% after CBF1. CBF2 was measured after 20 min during 2.5% sevoflurane. Finally, CO2-reactivity was studied in both groups. RESULTS: In group 1, no time-dependent alterations in CBF, CVR, ICP and CMRO2 were found. In group 2, an increase in sevoflurane from 1.5% to 2.5% resulted in an increase in CBF from 29 +/- 10 to 34 +/- 12 ml 100 g-1 min-1 and a decrease in CVR from 2.7 +/- 0.9 to 2.3 +/- 1.2 mmHg ml-1 min 100 g (P < 0.05), while ICP and CMRO2 were unchanged. CO2-reactivity was maintained at 1.5% and 2.5% sevoflurane. CONCLUSION: Sevoflurane is a cerebral vasodilator in patients with cerebral tumours. Sevoflurane increases CBF and decreases CVR in a dose-dependent manner. CO2-reactivity is preserved during 1.5% and 2.5% sevoflurane.

Adult↗