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Biomedical subjects

A Haase

Publications and source records attributed to A Haase.

At least 19 recordsLinked to original sources

Resistivity of red blood cells against high-intensity, short-duration electric field pulses induced by chelating agents.

The interaction of human red blood cells (RBCs) with diethylenetriamine-pentaacetic acid (DTPA) or its Gd-complex (Magnevist, a widely used clinical magnetic resonance contrast agent containing free DTPA ligands) led to the following, obviously interrelated phenomena. (i) Both compounds protected erythrocytes against electrohemolysis in isotonic solutions caused by a high-intensity DC electric field pulse. (ii) The inhibition of electrohemolysis was observed only when cells were electropulsed in low-conductivity solutions. (iii) The uptake of Gd-DTPA by electropulsed RBCs was relatively low. (iv) (Gd-) DTPA reduced markedly deformability of erythrocytes, as revealed by the electrodeformation experiments using high-frequency electric fields. Taken together, the results indicate that (Gd-) DTPA produce stiffer erythrocytes that are more resistant to electric field exposure. The observed effects of the chelating agents on the mechanical properties and the electropermeabilization of RBCs must have an origin in molecular changes of the bilayer or membrane-coupled cytoskeleton, which, in turn, appear to result from an alteration of the ionic equilibrium (e.g., Ca(2+) sequestration) in the vicinity of the cell membrane.

Chelating Agents

Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy.

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19-29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 +/- 1.2 and 5.3 +/- 1.2 mmol/kg wet wt (mean +/- SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed.

Adenosine Triphosphate

Fast T1 mapping on a whole-body scanner.

A method for the fast acquisition of quantitative T1 maps is presented. It is based on the acquisition of a series of snapshot fast low-angle shot (FLASH) images after inversion of the magnetization. A drawback of this method is the necessity for a sufficiently long relaxation delay before each inversion pulse, leading to long experimental times if averaging or segmentation is required. Thus implementation of this method on a whole-body scanner is problematic, as the longer gradient rise times provide prolonged repetition times, which makes segmentation indispensable to provide a sufficient temporal resolution. We present a modification of the method that allows for reduction in the intermediate relaxation delays and thus for considerably reduced experimental durations.

Artifacts

Perfusion-corrected mapping of cardiac regional blood volume in rats in vivo.

Measurement of regional blood volume (RBV) in the myocardium in vivo is important for the assessment of tissue viability and function. The method in this work is based on the acquisition of a T(1) map before and after intravascular contrast agent application. It is known that this method is influenced by perfusion that causes an overestimation of RBV values. In order to solve this problem, the new method is proposed which acquires T(1) maps with slice selective inversion pulses. Due to blood flow nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation time. A model that divides tissue into two compartments is adapted to slice selective inversion in order to derive a simple expression for perfusion-corrected RBV. The aim of the study is to demonstrate the feasibility and accuracy of this technique for quantification of RBV in rat myocardium in vivo. RBV maps were obtained for five rats, and the reproducibility was determined by repeating the experiment several times. A mean RBV value of 12.8 +/- 0.7% (v/v) over all animals was obtained in the myocardium. The results were compared with RBV maps obtained with perfusion-sensitive RBV imaging in the same five rats and with first-pass RBV studies. In order to demonstrate the strength of the new method the vasodilator adenosine was administered and alterations in microcirculation were imaged. Magn Reson Med 42:500-506, 1999.

Adenosine

Fast NMR flow measurements in plants using FLASH imaging.

A fast method for quantitative NMR imaging of flow velocities in intact plants is described. The purpose of this method is to observe dynamic changes of flow velocity in the xylem of plants after fast changes of environmental conditions. The spatial image resolution is 47 x 188 micrometer(2) in-plane. The method applies a fast gradient echo sequence (FLASH). Compared to other flow NMR imaging sequences, the imaging time was reduced by a factor of 6 with comparable signal-to-noise ratio. A complete flow measurement consists of a set of 8 different flow weighted images with a total acquisition time of 3.5 min.

Magnetic Resonance Spectroscopy

Signal intensities in FLASH-EPI-hybrid sequences.

Theoretical considerations on the signal-to-noise ratio (SNR) in FLASH-EPI-Hybrid imaging were published previously. The purpose of this work was to investigate in vivo the signal intensities in Hybrid images as a function of sequence specific parameters. In detail, the SNR as a function of the number of echoes m per RF excitation, the excitation flip angle alpha, and the dependence on the tissue relaxation times T1 and T2* were studied. In eight healthy subjects brain and abdominal Hybrid images were acquired where m and alpha were changed independently. Signal intensities in human brain, liver, and kidney were evaluated for each Hybrid experiment. Additionally, T1 and T2* values of these tissue types were quantified to allow for a comparison with the theory. An excellent agreement between calculated and measured signal behavior was found. The theory was therefore validated in vivo and can thus be used to optimize the signal-to-noise in Hybrid experiments.

Brain

Functional MR imaging of the human brain using FLASH: influence of various imaging parameters.

In this study the influence of a large variety of imaging parameters on the signal increase (DeltaS) and the contrast-to-noise ratio (CNR) of functional magnetic resonance imaging experiments was determined using FLASH imaging at 2 T. During visual stimulation of the brain we detected significant variations of DeltaS as a function of the echo time (30 ms: 3.5 +/- 0.4%, 60 ms: 6.8 +/- 0.7%), slice thickness (2.5 mm: 6.8 +/- 0.7%, 10.0 mm: 3.3 +/- 0.3%), and pixel size (4.69 mm: 3.1 +/- 0.3%, 1.88 mm: 5.9 +/- 0.5%). Significant changes of DeltaS with flip angle occurred for TE = 20 ms (15 degrees : 2.1 +/- 0.2%, 60 degrees : 3.2 +/- 0.5%). At TE = 30 ms there still was a slight increase (15 degrees : 3.0 +/- 0.4%, 60 degrees : 3.8 +/- 0.5%), while at TE = 50 ms no changes of DeltaS could be detected with flip angle. Furthermore, DeltaS decreased with the use of first-order flow and motion compensation (off: 5.8 +/- 0.6%, on: 4.5 +/- 0.5%). The purpose of this study was to identify the optimal imaging parameters for blood oxygenation level dependent contrast using FLASH imaging at 2 T. Relying on a time normalized contrast-to-noise ratio (CNR(n)) we found the following parameters to be optimal: TE approximately 40-50 ms, a rather low spatial resolution (slice thickness approximately 5.0-7.5 mm, pixel size approximately 2.3-4.6 mm, matrix size 64 x 48), and flip angles lower than 30 degrees. Flow compensation should not be applied, and a rather low bandwidth of approximately 2.5 kHz is favorable, as it yields a superior signal-to-noise ratio.

Adult

Laboratory analysis of superelastic NiTi compression springs.

The force/compression characteristics of 32 commercially available nickel titanium (NiTi) compression springs from seven distributors were investigated in vitro in order to support the orthodontist in deciding to select an appropriate spring for a given treatment. The geometrical properties of the coil springs, i.e., inner spring diameter, winding diameter and winding configuration, differed significantly, as well as the alloy composition and the thermo-mechanical treatment of the springs. All springs were mounted on a guiding rod made of an orthodontic steel wire (dimension: 0.016" x 0.022"), were compressed to a maximum extent and then relieved. Force/compression characteristics were measured at ambient temperatures of 27 degrees C, 37 degrees C and 47 degrees C. Three specimens were taken from each individual compression spring of a certain manufacturer and batch to check for constant material behaviour. A possible influence of sterilization on the mechanical properties of the compression springs was studied by autoclaving one spring of each manufacturer five times (6 minutes at 134 degrees C) and subsequently performing a force/deflection measurement. The NiTi compression springs were classified into three groups and covered a broad range of orthodontic forces between 0.5 N and 3.5 N. The width of the superelastic plateaus of the different NiTi coil springs reached from 0% to 66% of relative compression. An increase in the application temperature from 27 degrees C to 47 degrees C caused a rise in the height and a shortening of the width of the superelastic plateau. The resultant change in plateau force was as high as 0.4 N to 0.9 N, depending on the spring type investigated, the width of the plateaus was shortened by 4.0% to 15% of relative compression. All compression springs investigated displayed constant material behaviour within a certain batch. However, differences from one batch to another had a high level of significance. Forces on the plateau varied from one batch to the other by about +/-18%. An influence of sterilization on the force/compression behaviour could not be proved. Consequently, springs made of superelastic NiTi alloys cover a broad field of application with predefined and nearly constant force levels.

Analysis of Variance

Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression.

Herpesvirus gene expression can be classified into four distinct kinetic stages: latent, immediate early, early, and late. Here we characterize the kinetic class of a group of 16 Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies. Expression of two latent genes, LANA and vFLIP, was constitutive and was not induced by chemicals that induce the lytic cycle in primary effusion lymphoma (PEL) cell lines. An immediate-early gene, Rta (open reading frame 50 [ORF50]), was induced within 4 h of the addition of n-butyrate, and its 3.6-kb mRNA was resistant to inhibition by cycloheximide. Early genes, including K3 and K5 that are homologues of the "immediate-early" gene of bovine herpesvirus 4, K8 that is a positional homologue of Epstein-Barr virus BZLF1, vMIP II, vIL-6, and polyadenylated nuclear (PAN) RNA, appeared 8 to 13 h after chemical induction. A second group of early genes that were slightly delayed in their appearance included viral DHFR, thymidylate synthase, vMIP I, G protein-coupled receptor, K12, vBcl2, and a lytic transcript that overlapped LANA. The transcript of sVCA (ORF65), a late gene whose expression was abolished by Phosphonoacetic acid, an inhibitor of KSHV DNA replication, did not appear until 30 h after induction. Single-cell assays indicated that the induction of lytic cycle transcripts resulted from the recruitment of additional cells into the lytic cycle. In situ hybridization of KS biopsies showed that about 3% of spindle-shaped tumor cells expressed Rta, ORF K8, vIL-6, vMIP I, vBcl-2, PAN RNA, and sVCA. Our study shows that several KSHV-encoded homologues of cellular cytokines, chemokines, and antiapoptotic factors are expressed during the viral lytic cycle in PEL cell lines and in KS biopsies. The lytic cycle of KSHV, probably under the initial control of the KSHV/Rta gene, may directly contribute to tumor pathogenesis.

Chemokines

Expression of the open reading frame 74 (G-protein-coupled receptor) gene of Kaposi's sarcoma (KS)-associated herpesvirus: implications for KS pathogenesis.

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) encodes a G-protein-coupled receptor (GCR) homolog. This protein is a potent, constitutively active signalling molecule that can influence both proliferation and angiogenesis when ectopically expressed in fibroblasts in vitro. Here we have examined the expression of the KSHV GCR gene in virus-infected lymphoid cells and in KS tumors. Our results show that in both situations the gene is expressed primarily during lytic replication; its transcription is unaffected by inhibition of viral DNA synthesis, indicating that it is expressed in the early phases of the lytic program. The major transcript bearing GCR sequences is bicistronic, harboring coding sequences for another viral gene, K14, at its 5' end. Extensive searches for monocistronic GCR mRNAs using nuclease mapping and reverse transcription-PCR failed to detect such species. The 5' end of K14/GCR mRNA maps to nucleotide (nt) 127848, and its poly(A) addition site maps to nt 130546; a 149-nt intron is present in the K14/GCR intergenic region. These results suggest that the KSHV GCR is translated by unconventional mechanisms involving either translational reinitiation, internal ribosomal entry, or leaky ribosomal scanning. The restriction of GCR expression to the lytic cycle has important implications for the potential role(s) of the GCR in KS pathogenesis.

5' Untranslated Regions

Intestinal permeability and diarrhoeal disease in Aboriginal Australians.

BACKGROUND: Northern Territory Aboriginal children hospitalised with acute gastroenteritis have high rates of acidosis, hypokalaemia, and dehydration. AIMS: To determine whether Aboriginal children with and without diarrhoea have greater impairment in intestinal function than non-Aboriginal children, as assessed by increased permeability ratios. METHODS: A descriptive study of 124 children (96 Aboriginal and 28 non-Aboriginal) hospitalised with and without diarrhoea. Intestinal permeability was assessed by the lactulose to rhamnose (L-R) ratio from a five hour urine collection. RESULTS: In Aboriginal children, mean L-R ratios (95% confidence intervals) were 18.3 (17.1 to 19.6) with diarrhoea and 9.0 (7.3 to 11.0) without diarrhoea, and in non-Aboriginal children they were 5.9 (2.8 to 12. 3) and 4.2 (3.3 to 5.2), respectively. In patients with diarrhoea, L-R ratios were significantly raised when accompanied by acidosis (mean, 22.8; 95% CI, 17.0 to 30.5), hypokalaemia (mean, 20.7; 95% CI, 15.4 to 27.9), and >/= 5% dehydration (mean, 24.3; 95% CI, 19.0 to 29.6) compared with none of these complications (mean, 7.0; 95% CI, 3.5 to 13.8). CONCLUSION: The high incidence of acidosis, hypokalaemia, and dehydration in Aboriginal children admitted with diarrhoeal disease is related to underlying small intestinal mucosal damage.

Acidosis

Three-dimensional 31P magnetic resonance spectroscopic imaging of regional high-energy phosphate metabolism in injured rat heart.

The purpose of this study was to measure the spatially varying 31P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and 31P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.

Adenosine Triphosphate

Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse.

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.

Animals

Quantitative regional blood volume studies in rat myocardium in vivo.

Many pathophysiological processes in the myocardium are in close relation to changes of the regional blood volume and regional myocardial blood flow or perfusion. Only few methods exist to obtain quantitative values for these parameters. Quantitative regional blood volume (RBV) studies in rat myocardium are presented using snapshot fast low angle shot (FLASH) inversion recovery T1 measurements with two different blood pool contrast agents, gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA) albumin and Gd-DTPA polylysine. In contrast to previous attempts, each snapshot FLASH image acquisition was ECG-triggered under breathhold conditions. To measure relaxation times shorter than a heart cycle, each T1 sequence was repeated two times with different delays between inversion pulse and first image acquisition. The experiments were performed on a Bruker Biospec 70/21 using a homogeneous transmitter coil and a circularly polarized surface receiver coil, a special ECG trigger unit, and a respirator that is controlled by the pulse program. Based on a fast exchange model RBVm maps were calculated from the relaxation time maps for different concentrations of the two blood pool contrast agents. A significant dependence of the RBVm values on blood T1 was found. This is in accordance with a model that has been developed recently relating the dependence of RBVm on T1 of blood to perfusion. For Gd-DTPA albumin, the application of the model to the experimental data yields realistic values for RBV and perfusion. The values, which are in accordance with literature data, were obtained at highest contrast agent concentrations i.e., lowest relaxation times of blood (ca. 200 ms).

Albumins

Changes of myocardial high-energy phosphates with the cardiac cycle during acute or chronic myocardial stress.

Whether changes of cardiac high-energy phosphate concentrations occur over the cardiac cycle remains controversial. The hypothesis was that such cyclical changes are accentuated during acute or chronic myocardial stress. Isolated rat hearts were perfused under four conditions: (1) control, (2) inotropic stimulation by doubling of perfusate [Ca2+], (3) acute hypoxia (buffer PO2 approximately 150 torr), and (4) failing, chronically infarcted hearts. 31P-MR spectra were obtained at seven time points of the cardiac cycle. Under control conditions, cyclical changes ("cycling") of ATP (11+/-3%*, *P < 0.05) and phosphocreatine (9+/-2%*) were detected, inorganic phosphate cycling did not reach statistical significance. At high [Ca2+] perfusion, cycling of phosphocreatine (9+/-5%*) was not accentuated, cycling of ATP and inorganic phosphate did not reach significance. During acute hypoxia, cycling of ATP (10+/-4%*) and inorganic phosphate (11+/-4%*) occurred, but cyclical changes of phosphocreatine were not significant. In chronically infarcted hearts, the extent of cyclical changes of ATP, phosphocreatine, and inorganic phosphate was not accentuated. Thus, in perfused rat heart, small oscillations of high-energy phosphates during the cardiac cycle are detectable, but such changes are not accentuated during acute or chronic stress. The concentrations of high-energy phosphates over the cardiac cycle are tightly regulated.

Acute Disease

Endothelin-1 increases susceptibility of isolated rat hearts to ischemia/reperfusion injury by reducing coronary flow.

Endothelin-1 (ET-1) is the most potent vasoconstrictor known to date, and it was proposed that this peptide plays a major role in myocardial ischemia/reperfusion injury. ET-1 could increase myocardial susceptibility to ischemia by two mechanisms: via coronary flow reduction and/or via direct, metabolic effects on the heart. In isolated, buffer-perfused rat hearts, function was measured with a left ventricular balloon, and energy metabolism (ATP, phosphocreatine, inorganic phosphate, intracellular pH) was estimated by 31NMR-spectroscopy. Under constant pressure perfusion, hearts were subjected to 15 min of control perfusion, 15 ("moderate injury") or 30 ("severe injury") min of global ischemia, followed by 30 min of reperfusion. Hearts were pre-treated with ET-1 (boluses of 0.04, 4, 40 of 400 pmol) 5 min prior to ischemia. In the control period, ET-1 reduced coronary flow, ventricular function, phosphocreatine and intracellular pH dose-dependently: during ischemia/reperfusion, coronary flow, functional recovery and high-energy phosphate metabolism were adversely affected by ET-1 in a dose-related manner. To study effects of ET-1 not related to coronary flow reduction, additional hearts were perfused under constant flow conditions (ET-1 0 or 400 pmol) during 15 min of control, 15 min of ischemia and 30 min of reperfusion. When coronary flow was held constant, functional and energetic parameters were similar for untreated and ET-1 treated hearts during the entire protocol, i.e. the adverse effects of ET-1 on function and energy metabolism during ischemia/reperfusion were completely abolished. In both constant pressure and constant flow protocols, 400 pmol ET-1 reduced the extent of ischemic intracellular acidosis. The authors conclude that ET-1 increases the susceptibility of isolated hearts to ischemia/reperfusion injury via reduction of coronary flow.

Animals

Localized spectroscopy from anatomically matched compartments: improved sensitivity and localization for cardiac 31P MRS in humans.

Several pioneering studies have demonstrated that localized 31P NMR spectroscopy of the human heart might become an important diagnostic tool in cardiology. The main limitation is due to the low sensitivity of these experiments, allowing only crude spatial resolution. We have implemented a three-dimensional version of SLOOP ("spectral localization with optimal pointspread function") on a clinical instrument. SLOOP takes advantage of all available a priori information to match the size and the shape of the sensitive volumes to the anatomical structures in the examined subject. Thus, SLOOP reduces the contamination from adjacent organs and improves the sensitivity compared to conventional techniques such as ISIS or chemical shift imaging (CSI). Initial studies were performed on six healthy volunteers at 1.5 T. The good localization properties are demonstrated by the absence of resonances from blood in the heart spectra, and by PCr-free spectra from the liver. Compared to conventional CSI, the signal-to-noise ratio of the SLOOP heart spectra was improved by approximately 30%. Taking into account the varying excitation angle in the inhomogeneous B1 field of the surface coil, the SLOOP model computes the local spin saturation at every point in space. Therefore, no global saturation correction is required in the quantitative evaluation of local spectra. In this study, we found a PCr/gamma-ATP ratio in the left ventricular wall of 1.90 +/- 0.33 (mean +/- standard deviation).

Adenosine Triphosphate