Optimizing three-dimensional gadolinium-enhanced magnetic resonance angiography. Original investigation

RATIONALE AND OBJECTIVES: This primarily theoretical work examines three-dimensional gadolinium-enhanced magnetic resonance angiography f8p4Gd-MRA) with the goal of understanding how to achieve the best possible images with respect to signal to noise ratio (SNR) and k-space induced artifacts. Patient variables, contrast injection schemes, and pulse sequence parameters are considered for this purpose. METHODS: A theoretical analysis, including computer simulation, describes how contrast material injection profiles influence 3D Gd-MRA images, both in terms of intravascular signal and resultant artifacts. Further theoretical analysis of the spoiled gradient refocused pulse sequence describes how to maximize SNR. Clinical imaging complements computer modeling. RESULTS: Equations were derived relating contrast injection parameters and pulse sequence variables to SNR and artifacts. For present imaging equipment, administering contrast material over a duration of 60% to 80% of the total imaging time and using fractional echo techniques gives the best SNR without significantly sacrificing image quality. CONCLUSIONS: Three-dimensional Gd-MRA can be tailored to a specific clinical situation and imaging system through the use of proper breath-holding, bolus timing, Gd administration, and pulse sequence design.     

Age-related changes in compensatory stepping in response to unpredictable perturbations

BACKGROUND: Recent studies highlight the importance of compensatory stepping to preserve stability, and the spatial and temporal demands placed on the control of this reaction. Age-related changes in the control of stepping could greatly influence the risk of falling. The present study compares, in healthy elderly and young adults, the characteristics of compensatory stepping responses to unpredictable postural perturbations. METHODS: A moving platform was used to unpredictably perturb the upright stance of 14 naive, active and mobile subjects (5 aged 22 to 28 and 9 aged 65 to 81). The first 10 randomized trials (5 forward and 5 backward) were evaluated to allow a focus on reactions to relatively novel perturbations. The behavior of the subjects was not constrained. Forceplate and kinematic measures were used to evaluate the responses evoked by the brief (600 msec) platform translation. RESULTS: Subjects stepped in 98% of the trials. Although the elderly were less likely to execute a lateral anticipatory postural adjustment prior to foot-lift, the onset of swing-leg unloading tended to begin at the same time in the two age groups. There was remarkable similarity between the young and elderly in many other characteristics of the first step of the response. In spite of this similarity, the elderly subjects were twice as likely to take additional steps to regain stability (63% of trials for elderly). Moreover, in elderly subjects, the additional steps were often directed so as to preserve lateral stability, whereas the young rarely showed this tendency. CONCLUSIONS: Given the functional significance of base-of-support changes as a strategy for preserving stability and the age-related differences presently revealed, assessment of the capacity to preserve stability against unpredictable perturbation, and specific measures such as the occurrence or placement of multiple steps, may prove to be a significant predictor of falling risk and an important outcome in evaluating or developing intervention strategies to prevent falls.     

Bryostatin 1 induces ubiquitin COOH-terminal hydrolase in acute lymphoblastic leukemia cells

It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B-cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH-terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in morphology, surface immunophenotype, acid phosphatase and terminal deoxynucleotidyl transferase. Protein patterns of the parent and differentiated cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pl 34-5.3) was detected by 2 D PAGE in the differentiated, but not in parent cells. The presence of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2 D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in parent and Bryo1-treated cells and was compared with 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of ubiquitin expression as detected by flow cytometry. Sodium borohydride, an inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating effect is not fully understood. This study shows that UCH-L1 expression may play a major role in Bryo1-induced differentiation in pre-B-ALL.     

Frequency measurements of 9- and 10-μm N2O lasertransitions

We have measured frequencies of N₂O transitions by heterodyning sub-Doppler fluorescence-stabilized N₂O laser radiation with that from a reference CO₂ laser. A high-resolution cavity incorporates a ribbed tube and a highly reflective grating, permitting the CW oscillation of both the 10⁰ 0-02⁰0 9-μm and the 10⁰0-00⁰1 10-μm regular bands. This is the first sub-Doppler frequency measurement of the 9-μm band. The accuracy in the determination of the rotational constants for both bands has been improved by an order of magnitude, and calculated transition frequencies are presented     

New CO2 laser lines in the 11-μm wavelength region:new hot bands

Nineteen new laser lines in the 11-μm wavelength region have been observed in CW oscillation from a CO₂ laser with a high-Q, high-resolution cavity at a higher than usual current density. The frequency of each line has been measured using heterodyne frequency measurement techniques. Analysis of the frequencies shows that 15 lines are rotation-vibration transitions of the 01¹2-[11¹1,03¹1]_I band (the first sequence hot band) of the CO₂ molecule and four lines belong to the rotation-vibration transitions of the 02²1-[12 ²0, 04²0]_I band of CO₂     

Long-term effects of antihypertensive agents on proteinuria and renal function

BACKGROUND: Although many studies have examined the effects of antihypertensive agents on proteinuria and glomerular filtration rate in patients with kidney disease, many questions remain unresolved. These questions include whether the effects of agents differ, whether their effects are similar in diabetic and nondiabetic patients with renal disease, and whether the effects of any agents are independent of blood pressure reductions. METHODS: We conducted a meta-analysis of studies obtained with MEDLINE and bibliographies from comprehensive reviews but included only investigations with follow-up times of at least 6 months. We combined data (1) in an analysis of randomized controlled trials, (2) in a separate univariate analysis of controlled and uncontrolled trials, and (3) using weighted multiple linear regression. RESULTS: In 14 randomized controlled trials, angiotensin-converting enzyme inhibitors caused a greater decrease in proteinuria (pooled mean [95% confidence intervals], -0.51[-0.68 to -0.35], ln [treatment/control]), improvement in glomerular filtration rate (0.13 mL/min per month [0.10 to 0.16 mL/min per month]), and decline in mean arterial pressure (-4.0 mm Hg [-4.9 to -3.0 mm Hg]) compared with controls. In a multivariate analysis of controlled and uncontrolled trials, each 10-mm Hg reduction in blood pressure decreased proteinuria (regression coefficient [95% confidence interval] -0.14 [-0.22 to -0.06] ln [after/before]), but angiotensin-converting enzyme inhibitors (-0.45 [-0.58 to -0.32]) and nondihydropyridine calcium antagonists (-0.38 [-0.70 to -0.06]) were associated with additional declines in proteinuria that were independent of blood pressure changes and diabetes. Each 10-mm Hg reduction in blood pressure caused a relative improvement in glomerular filtration rate (0.18 mL/min per month [0.04 to 0.31 mL/min per month]), but among diabetic patients there was a tendency for dihydropyridine calcium antagonists to cause a relative reduction in glomerular filtration rate (-0.68 mL/min per month [-1.31 to -0.04 mL/min per month]). CONCLUSIONS: Long-term beneficial effects of antihypertensive agents on proteinuria and glomerular filtration rate are proportional to blood pressure reductions and are similar in diabetic and nondiabetic patients with renal disease. In addition, angiotensin-converting enzyme inhibitors, and possibly nondihydropyridine calcium antagonists, have additional beneficial effects on proteinuria that are independent of blood pressure reductions.     

A cytotoxic NK-cell line (NK-92) for ex vivo purging of leukemia from blood

Myeloablative chemo-/radiotherapy supported by transplantation of autologous bone marrow or blood progenitor cells for acute leukemia, lymphoma, or myeloma continues to be associated with a high relapse rate because of the infusion of malignant stem cells and the lack of an in vivo graft-vs.-leukemia (GVL) effect. Although various methods of purging are established for marrow, purging procedures for blood progenitor cell preparations have not been widely used primarily because of the technical challenges to process a higher number of cells. As a broadly applicable method for immunological purging, we tested whether highly cytotoxic cells from a natural killer (NK) cell line characterized previously (NK-92) could be used for immunological purging of blood preparations. The NK-92 cell line, which was established from a patient with non-Hodgkin's lymphoma, can lyse in vitro a broad range of leukemia, lymphoma, and myeloma cell lines even at very low effector:target (E:T) ratios; this lysis is superior to cytotoxicity obtained from normal peripheral blood mononuclear cells (PBMCs) stimulated for 4 days with interleukin (IL)-2. In an attempt to quantitate the purging achievable with NK-92 cells, normal PBMCs were spiked with 10% K562 cells that had been transfected with the neo(r) marker gene (K562-neo(r). Various numbers of NK-92 cells were then added to the cell mixtures, which were incubated for 4 or 48 hours at 37 degrees C with or without IL-2 (500 U/mL). In order to prevent their proliferation, NK-92 cells were irradiated with 1000 cGy (cesium source). This radiation dose was determined to suppress proliferation of NK-92 cells, but at the same time maintain full cytotoxic activity. After co-culture, the cells were plated in methylcellulose containing 0.8 mg/mL G418. The number of surviving K562-neo(r) colonies was counted under the microscope 7 days later and the results were considered a quantitative readout for the purging efficacy of NK-92 cells. No neomycin-resistant K562 colonies could be detected up to a ratio of NK-92:K562-neo(r) cells of 5:1 (effective NK-92:PBMC ratio of 0.5:1). The presence or absence of IL-2 during the culture period did not affect the results. At this ratio of NK-92:PBMC, the growth of normal clonogenic hematopoietic progenitor cells was not compromised as determined by a standard methylcellulose assay. Considering that K562 is a rapidly proliferating cell line and that the input number of K562 cells (10%) tested here was high, the data suggest that the cytotoxic NK-92 clone (after irradiation to prevent proliferation) could be used effectively for immunological ex vivo purging without compromising hematopoietic cell function.     

Transcriptional analysis of Marek''s disease virus (MDV) genes in MDV-transformed lymphoblastoid cell lines without MDV-activated cells

Prevention of the occurrence of diabetes-specific vascular complications is the final aim of clinical islet transplantation. Pancreatic islets isolated from adult pigs may be a suitable tissue source to transplant a large number of type 1 diabetic patients. Acute cellular rejection may be finally overcome by clinically applicable protocols for tolerance induction. However, primary nonfunction of the graft, as regularly observed in the porcine islet-to-rat xenotransplantation model, may be an additional problem. In this paper, species-specific inflammatory and immunological mechanisms are discussed which prevent early porcine islet graft function in rats but not in mice.     

Phase transformation and mechanical properties of si-free CMnAl transformation-induced plasticity-aided steel

Conventional CMnSi transformation-induced plasticity (TRIP)-aided steels are a promising solution for producing lighter, crash-resistant car bodies, due to their high-strength and large uniform elongation. The CMnSi TRIP-aided steels, with more than 1 mass pct Si, have the drawback of poor galvanizability due to the presence of complex Si-Mn oxides on the surface. The full substitution of the Si by Al in cold-rolled and intercritically annealed TRIP-aided steels, therefore, was evaluated in detail. The phase-transformation kinetics during the intercritical annealing and the isothermal bainitic transformation were investigated by means of dilatometry. The allotropic phase-boundary was determined both by thermodynamic calculations and the experimental determination of the C content in the retained austenite. The results imply that short isothermal bainitic transformation times are sufficient to obtain the TRIP microstructure and that the processing of CMnAl TRIP-aided steels in a continuous annealing line not equipped for overaging is possible. The mechanical properties were evaluated for CMnAl TRIP-aided steels obtained using an industrial thermal cycle: the properties matched those of the conventional CMnSi TRIP-aided steels, where it was found that the high-Al CMnAl TRIP-aided steel had a high strain-hardening coefficient of 0.25, which was stable up to a true strain of 0.25. on leave from the Yawata R&D Laboratory, Nippon Steel Corporation, Tobihata-cho, Japan. S. CLAESSENS, Product Research Manager, is with OCAS NV, Research Centre of the Sidmar Group, ARBED Group Flat Rolled Products Division, B-9060 Zelzate, Belgium.