Mikael Jensen

Quantification of liver fat using magnetic resonance spectroscopy.

Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.

Localized in vivo proton spectroscopy of the bone marrow in patients with leukemia

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate the haemopoietic (iliac bone) and fatty bone marrow (tibia) in patients with leukemia and polycythaemia vera. Selective measurements of the relaxation times T1 and T2 for the water and fat resonances in the bone marrow spectra were performed. Nine patients with acute leukemia and three patients with chronic leukemia were examined at diagnosis. Three patients with acute leukemia in remission were also examined. Five of the leukemic patients had follow-up examinations performed in relation to chemotherapeutic treatment. Nine patients with polycythaemia vera and 21 normal control subjects were examined with identical methods for comparison. All patients had bone marrow biopsies performed prior to every MR examination. Significant differences could be detected in the spectral patterns from iliac bone marrow in patients with leukemia at diagnosis compared to the healthy normal controls. The relative water content was increased in the iliac bone marrow spectra of the leukemic patients compared to the normal subjects, which indicates an increase in the amount of haemopoietic tissue and a corresponding decrease in marrow fat content. The T1 relaxation times of the water resonance in the spectra from the iliac bone marrow of the leukemic patients were significantly prolonged at diagnosis, compared to the normal controls and the patients with polycythaemia vera. After chemotherapeutic induction of remission, the spectra from the iliac bone marrow in the patients with leukemia resembled normal spectra. Four leukemic patients had abnormal spectra from the tibial bone marrow and one patient showed early changes in tibial marrow during chemotherapeutic treatment, before any major changes could be detected in the iliac bone marrow.

MR pulse sequences for selective relaxation time measurements: a phantom study.

The accuracy of relaxation time measurements of spectroscopic inversion recovery and CPMG multi-echo pulse sequences together with ISIS and stimulated echo-pulse methods have been tested on a reference phantom (test object no. 5, of the EEC Concerted Research Project). For the measurements a Siemens Magnetom wholebody magnetic resonance scanner operating at 1.5 Tesla was used. For comparison six imaging pulse sequences for relaxation time measurements were tested on the same phantom. The spectroscopic pulse sequences all had an accuracy better than 10% of the reference values.

Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days after the beginning of treatment, before any response was seen in the haemoglobin concentration of peripheral blood. The spectral changes indicate an alteration in cellular composition of haemopoietic bone marrow with an increase in the amount of haemopoietic active tissue. One patient showed a major change in the spectrum four days after treatment began, indicating that MR spectroscopy may detect early changes in the cellular composition of the bone marrow. This noninvasive method may be useful in evaluating treatment effects of recombinant human haemopoietic growth factors in the bone marrow, as well as investigating bone marrow response from different modes of rHuEPO administration.

Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease.

We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the hemoglobin concentration in peripheral blood. The increase in T1 relaxation times, together with earlier reported changes observed with localized magnetic resonance spectroscopy, indicate an alteration in cellular composition of the hemopoietic bone marrow with an increase in the amount of hemopoietic active tissue. MRI may be a useful, non-invasive way of evaluating bone marrow response to different modes of rHuEPO administration and dosage.

Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia.

BackgroundPreserved myocardial oxygen consumption estimated by carbon 11-acetate and positron emission tomography (PET) in myocardial regions with chronic but reversibly depressed contractile function in patients with ischemic heart disease have been suggested to be caused by repeated short episodes of acute myocardial ischemia. To evaluate this hypothesis myocardial 11C-acetate PET imaging was performed before and after acute repetitive myocardial ischemia.Methods and ResultsIn open chest dogs (n=8), the left anterior descending coronary artery was occluded 4 times for 5 minutes alternating with 5 minutes of reperfusion. Before and after repetitive coronary occlusions, oxygen 15 water/oxygen 15 carbon monoxide (blood flow), and 11C-acetate (oxygen consumption) PET imaging were performed. Left ventricular regional systolic wall thickening was measured with sonomicrometry. Forty-five minutes after the ischemic episodes, systolic ventricular wall thickening was decreased by 90%, whereas myocardial blood flow was reduced by 21% compared with baseline values (P<.05). Ninety minutes after the ischemic episodes, estimated oxygen consumption was unaltered compared with the baseline level despite a sustained 70% decrease in the regional contractile function (P<.05).ConclusionsOxygen consumption estimated by 11C-acetate PET imaging is preserved after repeated episodes of acute myocardial ischemia despite a severe impairment of contractile function.

Fluorodeoxyglucose uptake in dysfunctional myocardium subtended by an occluded coronary artery

Background. Myocardial segments with impaired function may have the potential for functional recovery. Augmented exogenous glucose uptake in relation to blood flow estimated by [2-18F]2-fluorodeoxyglucose (FDG) and positron emission tomography (PET) frequently indicates functional reversibility. The spectrum of FDG uptake levels in relation to Sestamibi uptake and dobutamine contraction reserve in areas with impaired function subtended by an occluded coronary artery has never been reported. Methods and results. Seventeen patients with stable angina pectoris and dysfunctional myocardium subtended by an occluded coronary artery were studied with FDG-PET, low-dose dobutamine echocardiography and Sestamibi - Single Photon Emission Computerized Tomography. In a 16 segment model dysfunctional myocardial segments showed a normally distributed FDG uptake ranging from 34% to 150% when normalized to peak segmental Sestamibi uptake. Low FDG uptake was associated with both lack of dobutamine induced contractile reserve and low Sestamibi uptake (in 73% of the segments) whereas high FDG uptake displayed both contractile reserve and Sestamibi uptake (57%). Segments with intermediate FDG uptake had either contractile reserve or a preserved Sestamibi uptake (62%). Conclusion. Dysfunctional myocardium subtended by an occluded coronary artery represents a continuum of metabolic states with a high degree of heterogeneity with regard to contractile reserve and Sestamibi uptake.

Reduced rate of uptake of zinc ions in a calf affected with the lethal syndrome A46 relative to clinically normal calves using whole body radio-isotope scanning of 62Zn

Four clinically healthy control calves were scanned and blood clearance was determined from blood samples taken during the first hour after intravenous injection of 62Zn. Furthermore, one clinically healthy control calf and one calf suffering from the lethal hereditary syndrome A46 were scanned and blood samples taken from five min after intravenous and abomasal injection of 62Zn and onwards for a period of up to 26th. The results show a very fast liver uptake of 62Zn. The estimated rate of plasma/blood clearance and liver uptake for the control calves agrees with values derived from studies on other animals. In contrast, the A46 calf had a decreased rate of plasma/blood clearance and liver uptake relative to the control calves.

Structure of Radical-Induced Cell Death1 Hub Domain Reveals a Common αα-Scaffold for Disorder in Transcriptional Networks

Communication within cells relies on a few protein nodes called hubs, which organize vast interactomes with many partners. Frequently, hub proteins are intrinsically disordered conferring multi-specificity and dynamic communication. Conversely, folded hub proteins may organize networks using disordered partners. In this work, the structure of the RST domain, a unique folded hub, is solved by nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, and its complex with a region of the transcription factor DREB2A is provided through data-driven HADDOCK modeling and mutagenesis analysis. The RST fold is unique, but similar structures are identified in the PAH (paired amphipathic helix), TAFH (TATA-box-associated factor homology), and NCBD (nuclear coactivator binding domain) domains. We designate them as a group the αα hubs, as they share an αα-hairpin super-secondary motif, which serves as an organizing platform for malleable helices of varying topology. This allows for partner adaptation, exclusion, and selection. Our findings provide valuable insights into structural features enabling signaling fidelity.

Spatial separation of the cyanogenic β-glucosidase ZfBGD2 and cyanogenic glucosides in the haemolymph of Zygaena larvae facilitates cyanide release

Low molecular weight compounds are typically used by insects and plants for defence against predators. They are often stored as inactive β-glucosides and kept separate from activating β-glucosidases. When the two components are mixed, the β-glucosides are hydrolysed releasing toxic aglucones. Cyanogenic plants contain cyanogenic glucosides and release hydrogen cyanide due to such a well-characterized two-component system. Some arthropods are also cyanogenic, but comparatively little is known about their system. Here, we identify a specific β-glucosidase (ZfBGD2) involved in cyanogenesis from larvae of Zygaena filipendulae (Lepidoptera, Zygaenidae), and analyse the spatial organization of cyanide release in this specialized insect. High levels of ZfBGD2 mRNA and protein were found in haemocytes by transcriptomic and proteomic profiling. Heterologous expression in insect cells showed that ZfBGD2 hydrolyses linamarin and lotaustralin, the two cyanogenic glucosides present in Z. filipendulae. Linamarin and lotaustralin as well as cyanide release were found exclusively in the haemoplasma. Phylogenetic analyses revealed that ZfBGD2 clusters with other insect β-glucosidases, and correspondingly, the ability to hydrolyse cyanogenic glucosides catalysed by a specific β-glucosidase evolved convergently in insects and plants. The spatial separation of the β-glucosidase ZfBGD2 and its cyanogenic substrates within the haemolymph provides the basis for cyanide release in Z. filipendulae. This spatial separation is similar to the compartmentalization of the two components found in cyanogenic plant species, and illustrates one similarity in cyanide-based defence in these two kingdoms of life.