Outer membrane protein (OMP) biogenesis in gram-negative bacteria is managed by a network of periplasmic chaperones that includes SurA, Skp, and FkpA. These chaperones bind unfolded OMPs (uOMPs) in dynamic conformational ensembles to suppress aggregation, facilitate diffusion across the periplasm, and enhance folding. FkpA primarily responds to heat-shock stress, but its mechanism is comparatively understudied.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2020
The periplasmic chaperone network ensures the biogenesis of bacterial outer membrane proteins (OMPs) and has recently been identified as a promising target for antibiotics. SurA is the most important member of this network, both due to its genetic interaction with the β-barrel assembly machinery complex as well as its ability to prevent unfolded OMP (uOMP) aggregation. Using only binding energy, the mechanism by which SurA carries out these two functions is not well-understood.
View Article and Find Full Text PDFSpeckle tracking echocardiography (STE) is increasingly used during functional assessments. However, reproducibility and dependence on echocardiographic image quality for speckle tracking stress echocardiography in pediatric patients have not been studied to date. 127 consecutive normotensive children without structural heart disease (mean age 13.
View Article and Find Full Text PDFBackground: Mitral annular plane systolic excursion (MAPSE) is an increasingly used echocardiography technique to assess left ventricular (LV) function. However, reproducibility and dependence on echocardiographic image quality for MAPSE in pediatric patients have not been studied to date.
Methods: We analyzed 284 transthoracic echocardiograms performed on consecutive normotensive children without structural heart disease (mean age 12.
Background: Data on left ventricular (LV) function in patients with neurocardiogenic syncope (NS) is conflicting in adults and lacking in children. The aim of this study was to analyze LV myocardial performance in children with NS at rest and during head-up tilt-table (HUTT) testing.
Methods: This is the first study to combine HUTT and speckle-tracking echocardiography (STE) in children with NS.
Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM).
View Article and Find Full Text PDFPurpose: KERMA ratios (RK) are defined as the ratio of KERMA measured at a specific phantom location (K) to in-air isocenter CT scanner output (KCT). In this work we investigate the impact of measurement methodology on KCT values.
Methods: OSL dosimeter chips were used to measure KCT for a GE VCT scanner (GE Medical Systems, Waukesha WI), using the 40 mm nominal beam width.
Background: Patient organ doses may be estimated from CTDI values. More accurate estimates may be obtained by measuring KERMA (Kinetic Energy Released in Matter) in anthropomorphic phantoms and referencing these values to free-in-air X-ray intensity.
Objective: To measure KERMA ratios (R(K)) in pediatric phantoms at CT.
Purpose: To estimate in-patient KERMA for specific organs in computed tomography (CT) scanning using ratios to isocenter free-in-air KERMA obtained using a Rando phantom.
Method: A CT scan of an anthropomorphic phantom results in an air KERMA K at a selected phantom location and air kerma K(CT) at the CT scanner isocenter when the scan is repeated in the absence of the phantom. The authors define the KERMA ratio (R(K)) as K∕ K(CT), which were experimentally determined in a Male Rando Phantom using lithium fluoride chips (TLD-100).
Rationale And Objectives: To evaluate the ability to view mediastinal and lung information on one window setting by processing images with a bilinear lookup table (LUT).
Materials And Methods: Chest computed tomography (CT) studies were obtained from 32 consecutive adult patient studies, which included 7 iodine contrast studies. From each CT examination, four sections were selected containing the suprasternal notch, carina, right inferior pulmonary vein, and the dome of the lower hemidiaphragm.
We investigated how patient head characteristics, as well as the choice of x-ray technique factors, affect lesion contrast and noise values in computed tomography (CT) images. Head sizes and mean Hounsfield unit (HU) values were obtained from head CT images for five classes of patients ranging from the newborn to adults. X-ray spectra with tube voltages ranging from 80 to 140 kV were used to compute the average photon energy, and energy fluence, transmitted through the heads of patients of varying size.
View Article and Find Full Text PDFWe investigated how patient age, size and composition, together with the choice of x-ray technique factors, affect radiation doses in head computed tomography (CT) examinations. Head size dimensions, cross-sectional areas, and mean Hounsfield unit (HU) values were obtained from head CT images of 127 patients. For radiation dosimetry purposes patients were modeled as uniform cylinders of water.
View Article and Find Full Text PDFPhysical characteristics were obtained for 196 patients undergoing chest and abdomen computed tomography (CT) examinations. Computed tomography sections for these patients having no evident pathology were analyzed to determine patient dimensions (AP and lateral), together with the average attenuation coefficient. Patient weights ranged from approximately 3 kg to about 120 kg.
View Article and Find Full Text PDFThe purpose of this study was to investigate how x-ray technique factors and effective doses vary with patient size in chest CT examinations. Technique factors (kVp, mAs, section thickness, and number of sections) were recorded for 44 patients who underwent a routine chest CT examination. Patient weights were recorded together with dimensions and mean Hounsfield unit values obtained from representative axial CT images.
View Article and Find Full Text PDFThe effect of rapid converting enzyme inhibition (CEI) with intravenous enalaprilat on technetium-99m-(99mTc) diethylenetriaminepentaacetic acid (DTPA) and 99mTc-dimercaptosuccinic acid (DMSA) renograms was evaluated in rats with two-kidney, one-clip renovascular hypertension. Rapid sequential DTPA renograms, performed immediately before and five minutes after enalaprilat injection (30 micrograms/kg), demonstrated a selective decrease in clipped kidney DTPA plasma clearance following CEI and no significant effect on unclipped kidney function. Pre- and post-CEI data were obtained with a single injection of DMSA by administering enalaprilat five minutes after the radiopharmaceutical.
View Article and Find Full Text PDFThe efficacy of five different radiodiagnostic agents for detecting renal tubular dysfunction induced with cisplatin in rats was compared to controls. Diethylenetriaminepentaacetic acid (DTPA) labeled with 99mTc or 111In was administered simultaneously with each of the other four agents [99mTc]glucoheptonate, [99mTc]dimercaptosuccinic acid, [131I]hippuran and [111In]lysozyme) as a standard to normalize for differences in functional impairment from animal to animal from the same dose of cisplatin. The 2-hr plasma clearance and computer-generated 2- to 3-min uptake in the two kidneys with [99mTc]dimercaptosuccinic acid were significantly inferior to similar measurements with the other agents in differentiating abnormal from normal function.
View Article and Find Full Text PDFThe efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included [99mTc]DTPA, [131I]hippuran, [111In]lysozyme, [99mTc]glucoheptonate (GHA), [99mTc]dimercaptosuccinate (DMS) and [111In]aminated dextran (amdex). A small dose of [99mTc]- or [111In]DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another.
View Article and Find Full Text PDFIn Goldblatt hypertension in rats produced by implanting a silver clip on the left renal artery, captopril induces a greater difference in the 1-min uptake of diethylenetriaminepentaacetic acid (DTPA) between the two kidneys than in baseline uptakes, similar to the experiences in unilateral renovascular hypertension in man. The combination of captopril and furosemide induces an even greater difference in renal uptakes than with captopril alone in this rat model. In paired experiments, DTPA complexes were used as a standard to compare the differences in renal uptake between the two kidneys after captopril-furosemide with other existing and potential renal radiodiagnostic agents.
View Article and Find Full Text PDFConventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v.
View Article and Find Full Text PDFDextrans with average molecular weights of 5,000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls.
View Article and Find Full Text PDFTo find a 99mTc agent with a high renal extraction efficiency similar to [131]hippuran, 21 analogs of DADS were labeled and evaluated. Preliminary screening by serial gamma camera imaging in rabbits showed that most analogs had a higher liver uptake and/or slower renal clearance, than hippuran. Three agents (P-DADS, AP-DADS, and CAP-DADS), exhibiting a relatively rapid blood clearance and lower liver uptake in the rabbit, were studied in greater detail in comparison with hippuran and CO2-DADS-A, the best analog to date.
View Article and Find Full Text PDFA pyridoxine (vitamin B6)-deficient diet in rats was used as a model of early renal lithiasis to find out if "stone-formers" could be identified from control animals by differences in the biodistribution of Tc-99m MDP. The mean renal uptake of this agent at 3 hours was about 70% higher in test animals than in controls, but there was considerable overlap between the upper limits of the normal range and lower values in "stone-formers." If these results were valid for humans, the metabolic abnormality in males with early stone-forming disease could not be identified with certainty by in vivo measurements of Tc-99m MDP renal uptake alone.
View Article and Find Full Text PDFThe 3-hour biodistribution of 99mTc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. 95mTc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney.
View Article and Find Full Text PDFIncreased renal uptake of 99mTc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels.
View Article and Find Full Text PDFThe renal extraction efficiencies for various radioactive agents were measured in normal anesthetized dogs during 1 hr after a single intravenous injection. Radioassays were made on serial blood samples drawn simultaneously from the aorta upstream from the renal arteries and from one renal vein. As a reference substance [131I]o-iodohippurate was injected concurrently in all experiments.
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