Biomedical subjects

Søren Christensen

Publications and source records attributed to Søren Christensen.

11 recordsLinked to original sources

PubMed2006

Characterizing physiological heterogeneity of infarction risk in acute human ischaemic stroke using MRI.

Viable tissues at risk of infarction in acute stroke patients have been hypothesized to be detectable as volumetric mismatches between lesions on perfusion-weighted (PWI) and diffusion-weighted magnetic resonance imaging (DWI). Because tissue response to ischaemic injury and to therapeutic intervention is tissue- and patient-dependent, changes in infarct progression due to treatment may be better detected with voxel-based methods than with volumetric mismatches. Acute DWI and PWI were combined using a generalized linear model (GLM) to predict infarction risk on a voxel-wise basis for patients treated either with non-thrombolytic (Group 1; n = 11) or with thrombolytic therapy (Group 2; n = 27). Predicted infarction risk for both groups was evaluated in four ipsilateral regions of interest: tissue acutely abnormal on DWI (Core), tissue acutely abnormal on PWI but normal on DWI that either infarcts (Recruited) or does not (Salvaged), and tissue normal on both DWI and PWI that does not infarct (Normal) by follow-up imaging > or = 5 days. The performance of the models was significantly reduced for the thrombolysed group compared with the group receiving standard treatment, suggesting an alteration in natural progression of the ischaemic cascade. Average GLM-predicted infarction risk values in the four regions were different from one another for both groups. GLM-predicted infarction risk in Salvaged tissue was significantly higher (P = 0.02) for thrombolysed patients than for non-thrombolysed patients, suggesting that thrombolysis rescued tissue with higher infarction risk than typically measured in tissue that spontaneously recovered. The observed spatial heterogeneity of GLM-predicted infarction risk values probably reflects the varying degrees of tissue injury and salvageability that exist after stroke. MRI-based algorithms may therefore provide a more sensitive means for monitoring therapeutic effects on a voxel-wise basis.

Acute Disease↗

PubMed2006

Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives.

Carbamylerythropoietin (CEPO) does not bind to the classical erythropoietin (EPO) receptor. Nevertheless, similarly to EPO, CEPO promotes neuroprotection on the histologic level in short-term stroke models. In the present study, we investigated whether CEPO and other nonerythropoietic EPO analogs could enhance functional recovery and promote long-term histologic protection after experimental focal cerebral ischemia. Rats were treated with the compounds after focal cerebral ischemia. Animals survived 1, 7, or 60 days and underwent behavioral testing (sensorimotor and foot-fault tests). Brain sections were stained and analyzed for Iba-1, myeloperoxidase, Tau-1, CD68 (ED1), glial fibrillary acidic protein (GFAP), Fluoro-Jade B staining, and overall infarct volumes. Treatment with CEPO reduced perifocal microglial activation (P<0.05), polymorphomonuclear cell infiltration (P<0.05), and white matter damage (P<0.01) at 1 day after occlusion. Carbamylerythropoietin-treated rats showed better functional recovery relative to vehicle-treated animals as assessed 1, 7, 14, 28, and 50 days after stroke. Both GFAP and CD68 were decreased within the ipsilateral thalamus of CEPO-treated animals 60 days postoperatively (P<0.01 and P<0.05, respectively). Furthermore, behavioral analysis showed efficacy of CEPO treatment even if administered 24 h after the stroke. Other nonerythropoietic derivatives such as carbamylated darbepoetin alfa and the mutant EPO-S100E were also found to protect against ischemic damage and to improve postischemic neurologic function. In conclusion, these results show that postischemic intravenous treatment with nonerythropoietic EPO derivatives leads to improved functional recovery, which may be linked to their long-term effects against neuroinflammation and secondary tissue damage.

Animals↗

PubMed2006

Automatic selection of arterial input function using cluster analysis.

Quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast MRI requires determination of the arterial input function (AIF) representing the delivery of intravascular tracer to tissue. This is typically accomplished manually by inspection of concentration time curves (CTCs) in regions containing the ICA, VA, and MCA. This is, however, a time consuming and operator dependent procedure. We suggest a completely automatic procedure for establishing the AIF based on a cluster analysis algorithm. In 20 normal subjects CBF maps calculated in 2 slices by the automatic procedure were compared to maps obtained with AIFs selected individually by 7 experienced operators. The average manual to automatic CBF ratio was 1.03+/-0.15 in the lower slice and 1.05+/-0.12 in the upper slice, demonstrating excellent agreement between the manual and automatic method. The algorithm provides means for objectively assessing AIF candidates in local AIF search algorithms designed to reduce bias due to delay and dispersion. Given the reproducibility and speed (10 s) of the automatic method, we speculate that it will greatly improve the accuracy of perfusion images and facilitate their use in clinical diagnosis and decision-making, particularly in acute stroke but also in cerebrovascular disease in general.

Aged↗

PubMed2006

Dopamine storage capacity in caudate and putamen of patients with early Parkinson's disease: correlation with asymmetry of motor symptoms.

Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [(18)F]fluorodopa (FDOPA) assumes irreversible trapping of [(18)F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [(18)F]fluorodopamine from the brain (k(loss)), from which can be calculated an effective distribution volume (EDV(1)), which is an index of [(18)F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k(loss) and EDV, here defined as EDV(2). This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k(loss) and EDV(2) were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV(2) were most sensitive for discrimination of PD and normal putamen. However, k(loss) was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k(loss) also detected in the caudate of PD patients a decline in the retention of [(18)F]fluorodopamine relative to healthy aged control subjects.

Aged↗

PubMed2005

Ischemic injury detected by diffusion imaging 11 minutes after stroke.

A 78-year-old woman suffered a stroke inside a magnetic resonance scanner while being imaged because of a brief transient ischemic attack 2 hours earlier. Diffusion-weighted images obtained 11 minutes after stroke showed tissue injury not found on initial images. The data show early, abrupt diffusion changes in hypoperfused tissue, adding to our understanding of the progression of microstructural abnormalities in the hyperacute phase of stroke.

Aged↗

PubMed2005

Cloning, expression and characterization of a sialidase gene from Arthrobacter ureafaciens.

Sialidases have recently been used in the processing of clinically relevant asialoproteins. The Arthrobacter ureafaciens sialidase (EC 3.2.1.18) exhibits broad substrate specificity and is often used in such applications. We have employed an expression cloning strategy to isolate the A. ureafaciens sialidase. The clone encodes a 990-amino-acid 104 kDa open-reading-frame protein containing three domains: an N-terminal catalytic domain, a linker domain with an immunoglobulin-like fold and a C-terminal domain of unknown function. Expression in Escherichia coli indicates that the sialidase promoter was active in E. coli. Overexpression in E. coli resulted in several truncated forms. A 54 kDa truncated variant was generated, expressed and purified, and its feasibility for use in an erythropoietin desialylation process was demonstrated.

Amino Acid Sequence↗

PubMed2004

Aphid effects on rhizosphere microorganisms and microfauna depend more on barley growth phase than on soil fertilization.

This paper gives the first reports on aphid effects on rhizosphere organisms as influenced by soil nutrient status and plant development. Barley plants grown in pots fertilized with N but without P (N), with N and P (NP), or not fertilized (0) were sampled in the early growth phase (day 25), 1 week before and 1 week after spike emergence. Aphids were added 16 days before sampling was carried out. In a separate experiment belowground respiration was measured on N and NP fertilized plant-soil systems with aphid treatments comparable to the first experiment. Aphids reduced numbers of rhizosphere bacteria and fungal feeding nematodes 1 week before spike emergence. Before spike emergence, aphids reduced belowground respiration in NP treatments. These findings strongly indicate that aphids reduced allocation of photoassimilates to roots and deposition of root exudates in the growth phase of the plant. Contrary to this, 1 week after spike emergence numbers of bacteria, fungal feeding nematodes and Protozoa were higher in rhizospheres of plants subjected to aphids probably because aphids enhanced root mortality and root decomposition. Protozoa and bacterial feeding nematodes were stimulated at different experimental conditions with nematodes being the dominant bacterial grazers at N fertilization and Protozoa in the NP treatment before spike emergence.

Analysis of Variance↗

PubMed2004

Derivatives of erythropoietin that are tissue protective but not erythropoietic.

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

Animals↗

PubMed2004

Quantitative cerebral perfusion using the PRESTO acquisition scheme.

PURPOSE: To evaluate the feasibility of using the rapid principles of echo shifting with a train of observations (PRESTO) sequence for measurements of cerebral hemodynamic parameters based on first pass of a contrast agent. MATERIALS AND METHODS: Simulations were performed to investigate potential resolution loss due to relaxation effects. Experimental evaluation was conducted in healthy monkey brains using PRESTO and echo-planar imaging (EPI). RESULTS: For short echo trains, an insignificant contribution of the longitudinal and transversal relaxation rates to the signal amplitude in white matter and gray matter was found, whereas a contribution as large as 40% was found in large vessels. Simulations of the point spread function demonstrated that PRESTO, despite its shorter readout trains, only has a small advantage in terms of maintenance of image resolution during bolus passage compared to EPI as long as the EPI echo train can be kept similar to the T2* value at the top of the bolus. Experimental studies revealed that the PRESTO and EPI gray matter to white matter ratio were similar with respect to cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). CONCLUSION: The study showed that PRESTO and EPI led to comparable quantitative perfusion parameters.

Animals↗

PubMed2004

Repressive coping before and after diagnosis of breast cancer.

OBJECTIVE: The aim was to investigate to which extent emotional repression is a premorbid coping tendency of cancer patients and/or a coping response to the threat posed by a cancer diagnosis. The results of one previous study of breast cancer patients suggest the latter possibility, and our aim was to replicate and extend these findings. METHODS: Of 646 women referred to mammographic examination for breast cancer, 71 women were diagnosed with primary breast cancer. Repressive coping, defined as having high scores on defensiveness (Marlowe-Crowne Social Desirability Scale) and low scores on anxiety (Taylor Manifest Anxiety Scale), was measured (1) before, (2) 4 weeks after, and (3) 12 weeks after diagnosis. The women were not aware of their disease status before the examination, and there were no significant differences between groups in their perceived risk of having breast cancer. RESULTS: Four weeks after diagnosis, increased repression (p < 0.01) was found in the group of women diagnosed with breast cancer but not in women without cancer, with women with a breast cancer diagnosis being 1.5 times more likely to be repressive than women with cancer. There were no group differences in defensiveness, anxiety, or repression before diagnosis and 12 weeks after diagnosis. When controlling for repressive coping prior to diagnosis, age, and other demographic factors with a multiple, logistic regression, only cancer diagnosis (odds ratio: 2.39; p< 0.05) and having biological children (odds ratio: 2.83; p< 0.02) emerged as significant predictors of repressive coping 4 weeks after diagnosis. Before diagnosis, only higher age predicted later diagnosis of breast cancer. CONCLUSION: Previously found higher repression in cancer patients vs. controls could be a response to the threat associated with cancer diagnosis and may not necessarily reflect premorbid differences.

Adaptation, Psychological↗

PubMed2003

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did not increase the hematocrit of mice or rats. AsialoEPO appeared promptly within the cerebrospinal fluid after i.v. administration; intravenously administered radioiodine-labeled asialoEPO bound to neurons within the hippocampus and cortex in a pattern corresponding to the distribution of the EPO receptor. Most importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection.

Animals↗