Application of region of interest definition to quadtree-based compression of CT images.

A quadtree-based data compression algorithm can provide different levels of compression within and outside of regions of interest (ROIs). The current study shows whether ROI compression can provide greater compression or diagnostic accuracy than uniform quadtree compression. In 75 single CT images from 75 consecutive abdominal examinations, 43 abnormalities were identified and surrounded by ROIs. Three radiologists interpreted the images following (1) 50:1 compression of the entire image; (2) ROI compression at five decreasing compression ratios (with 50:1 compression outside the ROI); and (3) reversible (lossless) compression of the entire image. Reversible compression (compression ratio 3:1) yielded a sensitivity of 96%. ROI compression of 15:1 was achieved with no loss of sensitivity; ROI compression of 28:1 yielded a sensitivity of 91% (not significantly different). At any given compression ratio, diagnostic sensitivity was greater with ROI compression than with uniform quadtree compression. For purposes of image archiving, quadtree-based ROI compression is superior to uniform compression of CT images.

Quadtree-based data compression of abdominal CT images.

An ROC study was performed to evaluate the effect of quadtree-based data compression on the diagnostic yield of CT images. Seventy images were selected from a series of consecutive abdominal/pelvic CT scans. Following the application of quadtree-based compression, all images were reviewed independently by three radiologists. The images were analyzed at six decreasing irreversible compression ratios (30.6:1 to 7.4:1), as well as after reversible compression (2.9:1). ROC curves reveal a gradual decrease in clinical accuracy with increasing compression ratios. At a compression ratio of 7.4:1, sensitivity for all major abnormalities was 99% with a specificity of 93%. As the compression ratio was increased to 30.6:1, sensitivity and specificity dropped to 75% and 83% respectively. Execution times for compression and decompression of the CT images with a PC-AT based digital radiography system varied from 24.7 to 18.5 seconds and from 16.2 to 5.1 seconds respectively, decreasing with higher levels of compression. We conclude that quadtree-based compression of abdominal CT images may have practical applications for a PC based digital radiography system.

Pneumoperitoneum resembling air in the biliary tree: CT features.

The various CT appearances of free abdominal air have been described. We present a hitherto undescribed CT manifestation of this condition. When subhepatic free air tracks along the porta hepatis and suspensory ligaments of the liver, it may resemble biliary air.

Evaluation of a quadtree-based compression algorithm with digitized urograms.

The effect of a quadtree-based data-compression algorithm on the diagnostic yield in digitized radiographs was studied for 100 urograms. Each image was digitized and reviewed at nine decreasing compression ratios ranging from 90:1 to 4.2:1, followed by a review of the uncompressed digital images. Four radiologists independently reviewed the digitized images and the original radiographs and agreed on a reference standard of 201 findings. Sensitivity, measured by the number of findings noted on the compressed digital images, decreased with increasing compression ratios at and above the 11:1 level. No loss of sensitivity was noted with a compression ratio of 4.2:1. Sensitivity decreased more precipitously for calcifications than for soft-tissue masses. Only a minimal loss of sensitivity for bilateral renal function was noted, even with high compression ratios. False-positive rates were unaffected by compression. The authors conclude that quadtree compression ratios of 11:1 and higher may result in loss of sensitivity in clinically relevant findings.

MR imaging of portal vein thrombosis.

MR imaging is emerging as a potential means of detecting portal venous thrombosis (PVT). Therefore, we attempted to establish specific criteria with which to diagnose PVT on conventional spin-echo images. In a retrospective review of 342 consecutive abdominal MR scans performed with a 0.5-T magnet, we identified nine patients with persistent signal in the portal vein and used the findings in these patients to establish criteria with which to diagnose PVT. We subsequently applied these criteria to 109 additional consecutive abdominal MR scans performed with the same magnet. Fifteen cases were found in which all images showed either (1) signal involving the entire width of the portal vein lumen, which approximated (with T1 weighting) and exceeded (with T2 weighting) the intensity of the hepatic parenchyma in images in which the hepatic veins showed a complete flow void or (2) complete nonvisualization of the portal vein and its major branches in images that showed a flow void in portal venous collaterals and hepatic veins. All patients had unequivocal findings of PVT on at least one other imaging study (CT or sonography) or at surgery. Although the sensitivity of these signs could not be calculated, their specificity was 100%. We conclude that in the presence of these signs, the diagnosis of PVT can be made with confidence.

Two pathways for oxygen exchange by heavy meromyosin and their dependence on actin.

In the hydrolysis of MgATP by acto heavy meromyosin (HMM) there are two enzymatic pathways that differ in the properties of their intermediate oxygen exchange; one of these is designated the low exchange pathway (P1); the other is designated the high exchange pathway (P2). A plot of the P1 flux versus the actin concentration gives a sigmoid curve, whereas the corresponding curve for the P2 flux rises in an approximately hyperbolic manner. At low concentrations of actin, where the sigmoid curve of the P1 flux is in a lag phase, the major flux is along P2; but at higher concentrations of actin, as the P1 curve rises sharply, the flux along P1 comes to predominate. Even at the highest levels of actin, at saturating levels for both pathways, the kinetics of exchange along P1 and P2 are significantly different. In addition to these differences in the actin dependence, the flux of P1 relative to P2 is markedly inhibited by KCl. Therefore, which of the two pathways dominates during the hydrolysis of MgATP by HMM is strongly dependent on experimental conditions. The findings suggest that P1 involves the interaction of HMM with two actin units whereas P2 involves the interaction of HMM with one actin unit. The results are discussed in relation to a kinetic scheme based on this proposal.

Dental considerations for the patient receiving dialysis for renal failure.

A review of the literature describing the dental management of patients receiving hemodialysis because of renal failure is presented. A description of the renal failure process is given. Pretreatment and day of treatment precautions are considered. A pertinent dental case report of a dialysis patient is also presented.

The two pathways for oxygen exchange by actomyosin and myofibrils and their dependence on temperature.

At an intermediate stage in the hydrolysis of MgATP by actomyosin there is an exchange of oxygen between water and the terminal phosphoryl group of MgATP, tightly bound to the myosin active site. This intermediate oxygen exchange results from the reversible hydrolysis of the bound MgATP. The rate of the exchange cycle (hydrolysis and the reverse) is assumed to be determined by the rate of reverse hydrolysis; and the average time available for exchange is determined by the post-exchange reaction that immediately follows the cycle. Past analytical studies of the exchange, using actomyosin mixtures and myofibrils at room temperature, have revealed two pathways for hydrolysis, operating at a comparable flux but differing greatly in the extent of exchange they support. It is shown here that these pathways also appear over a range of temperatures from 5 to 30 degrees C and that temperature had little effect on their relative fluxes. At each temperature, the flux ratio (%) for the low exchange pathway: high exchange pathway was near 50:50 for actomyosin mixtures and 60:40 for myofibrils. Apparently, the rate-limiting steps that determine the fluxes of the two pathways have a similar temperature dependence. However, the analysis indicates that one or both of the steps that determine the extent of exchange (reverse-hydrolysis and/or the post-exchange reaction) shows a different temperature dependence for the two pathways. We interpret this to reflect a difference in the temperature dependence of the post-exchange reaction, which we propose is exceedingly fast and independent of actin concentration along the low exchange route, but slow and dependent on the actin concentration along the high exchange route. Thus at all temperatures over a broad range of actin concentration there are two pathways of comparable flux that differ primarily in the time available for exchange.

Hepatic uptake of technetium-99m diphosphonate in thalassemia major.

Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions.

Evidence from oxygen exchange studies that the two heads of myosin are functionally different.

Recent studies of oxygen exchange have shown that there are two normal pathways for the hydrolysis of MgATP by myosin in the presence of actin, each producing Pi at the same rate. These two apparent pathways for actin-activated hydrolysis differ greatly in the extent of oxygen exchange they support. This is revealed by an analysis of the distribution of [18O]Pi species produced by the hydrolysis of [gamma-18O]ATP. We have extended these studies to certain abnormal substrates, using Mn2+ in place of Mg2+, and dATP or ITP in place of ATP. The results, together with past findings, lead to the proposal that the two heads of myosin are functionally different. One of these (Head 1) is able to reversibly cleave bound MgATP and thereby support oxygen exchange while it is free of actin; the other (Head 2) cannot cleave bound MgATP at its active site while free of actin. However, in the presence of actin, both Head 1 and Head 2 cleave bound MgATP, support some oxygen exchange, and produce Pi at the same rapid actin-activated rate. Apparently, MgATP is positioned differently on the two heads when they are free of actin, with Mg2+ and the 6-amino group of ATP playing an important role in the orientation. This proposed difference between the heads could serve to make Head 1 react first with the actin filament, followed by Head 2. Thus, in muscle, the two heads on a myosin cross-bridge would interact with an actin filament and exert their pull in a fixed sequence.

Oxygen-exchange studies on the pathways for magnesium adenosine 5'-triphosphate hydrolysis by actomyosin.

At an intermediate stage in the hydrolysis of magnesium adenosine 5'-phosphate (MgATP) by myosin or actomyosin, there is an exchange of oxygen between water and the P gamma group of enzyme-bound nucleotide. Starting with [P gamma-18O]ATP as substrate, the exchange is revealed in the [18O]Pi species that are ultimately released as product into the reaction medium. An analysis of the distribution of these labeled Pi species, which contain 3, 2, 1, or none of the 18O atoms originally on the P gamma of ATP, is used to probe intermediate stages of the hydrolytic mechanism. In recent years, studies of this kind by several groups have shown that more than one pathway of hydrolysis operates. The work reported here demonstrates that two of these pathways are spurious; one is a "nonexchanging MgATPase" that is present in fresh myosin preparations; the other is an induced slow exchange that develops in myosin during storage (-20 degrees C) and subsequent aging (4 degrees C). However, after correction for these artifacts, two normal pathways for actomyosin hydrolysis remain. These normal pathways differ in the mode of interaction between actin and myosin in the course of hydrolysis; one is the Lymn-Taylor pathway where oxygen exchange occurs at a stage when actin and myosin are dissociated; the other is a pathway in which actin and myosin are associated during oxygen exchange. Each of these two pathways contributes an equal amount of Pi to the product pool. Thus, on average, each myosin head uses each of these pathways half the time. The findings suggest, e.g., that during contraction, myosin can dissociate from the actin filament only during every other cycle of MgATP hydrolysis or that only half the heads, at any one time, can exchange oxygen while free of the actin filament.

Inhibition of oxygen exchange by chemical modifiers at the sulfhydryl 1 or reactive lysine residue of myosin. Changing the rates of intermediate enzymatic reactions by modifying the course of reaction-linked conformational changes.

During the hydrolysis of MgATP by myosin, there is an extensive exchange of oxygen between water and the terminal phosphate group of bound nucleotide, which results from a repeated cycle of hydrolytic cleavage and its reversal. An analysis of the distribution of [18O]Pi species from the hydrolysis of [gamma-18O]ATP gives an estimate for the apparent rate constant [k-3(app)] of reverse cleavage, which is the rate-limiting step of the exchange cycle. We have performed this kind of analysis with two different forms of modified myosin, containing either N-ethylmaleimide at the sulfhydryl 1 group or trinitrophenyl at the reactive lysine residue. Although these modifications of the protein are chemically different, and the sulfhydryl 1 group and the reactive lysine residue are far apart in the primary chain of the myosin head, the two modifications caused a similar marked inhibition of oxygen exchange. This effect resulted from: 1) a decrease in the time available for the exchange cycle due to a 3-10-fold increase in the turnover rate of hydrolysis and 2) a reduction in k-3 (app) from 2-5 s-1 to 0.2-0.5 s-1. It is proposed that modifications of this type influence enzymatic activity by altering the course of "reaction-linked conformational changes," i.e. those changes in protein structure that are coupled to the catalytic mechanism but are not part of the substrate-binding site proper. It is also suggested that certain naturally occurring protein modifications, e.g. methylation of histidine or lysine residues, could regulate function by operation of this mechanism.

Studies on the special properties of actomyosin in the gel form. I. Unusual features of the Mg2+-ATPase activity.

The hydrolysis of MgATP by actomyosin gel at low ionic strength is known to show two unusual features: (1) an Arrhenius plot with a shallow slope in the higher temperature range (35-16 degrees C) and a steep slope in the lower temperature range (16-0 degrees C); (2) a rate curve of hydrolysis that begins with a 'burst' and falls to a lower steady-state level. Both of these can now be interpreted in terms of a specific, relatively slow transformation in the gel (t 1/2 = 9 s at 25 degrees C), induced by the binding of MgATP to the active sites of the myosin filaments. In the rate curves, this transformation is reflected in the transition from the burst rate (catalyzed by the original gel) to the steady-state rate (catalyzed by the modified gel). Importantly, this transition does not occur to a significant extent at low temperatures. Thus, in the typical nonlinear Arrhenius plot, where steady-state rates are used, the shallow slope in the high temperature range is a property of the modified gel, whereas the steep slope at low temperatures is a property of the original gel. Consistent with this interpretation, when the burst rates (presumably due to the original gel) were used in the high temperature range (and when substrate inhibition of hydrolysis by high levels of MgATP was avoided), the Arrhenius plot was linear over the entire temperature range (40-0 degrees C); the steep slope of this plot gives a high apparent heat of activation (25-30 kcal), similar to that reported for actin-activated hydrolysis by the soluble subfragment, heavy meromyosin. It is the steady-state form of the gel at high temperatures that gives a low apparent heat of activation (6-10 kcal). It was found that the regulatory proteins with calcium activate hydrolysis by the original form but have no effect on the steady-state form of the gel. Oxygen exchange measurements made during the burst and steady state at 25 degrees C indicate that the mechanism of hydrolysis is essentially the same for both, but that there is a higher effective actin concentration around the myosin sites in the original form.

Studies on the special properties of actomyosin in the gel form. II. An analysis of the turbidity changes seen in gel suspensions.

The turbidity changes induced by MgATP in suspensions of actomyosin gel particles have been studied systematically over a wide range of MgATP concentrations at different temperatures with and without the regulatory proteins. An analysis of these changes distinguishes three separate protein-protein interactions in the gel: (1) The transient cyclic interactions between actin and myosin involved in the hydrolysis of MgATP and contraction. (2) Cross-links that cause turbidity in the original suspension. (3) Cross-links that cause the high turbidity usually associated with superprecipitation. In general, there was a good correlation between the half-time for reaching maximum turbidity during superprecipitation and the rate of hydrolysis. On the other hand, the actual magnitude of the turbidity increase was progressively diminished as the concentration of substrate was raised in the millimolar range. It appears that some essential phase of the superprecipitation process is limited by the same enzymatic step that limits the rate of hydrolysis. However, whether or not this phase leads to an increase in turbidity depends on the concentration of MgATP. Apparently, high physiological levels of MgATP (1-5 mM) inhibit the formation of the specific cross-links that cause high turbidity in the superprecipitate. It is proposed that MgATP interferes with these links when it can bind to a low-affinity site on myosin that is separate from the high-affinity active sites for hydrolysis. Thus, in contracting muscle, interfilament interactions analogous to those that increase turbidity and cause isodimensional shrinkage in the gel would be prevented by the high level of MgATP in the sarcoplasm. Observations relating the shortening of isolated myofibrils to their turbidity in suspension lend support to this interpretation.

Serum ferritin as a guide to therapy in neuroblastoma.

Elevated serum ferritin levels without a corresponding increase in tissue iron storage have been observed in patients with certain cancers. Increased synthesis of ferritin by cancer cells has also been reported. In order to see whether similar phenomena occurred in patients with neuroblastoma, we have screened serum ferritin levels in 58 children with neuroblastoma by counterelectrophoresis using antibody to human ferritin. Increased ferritin levels in serum, positive by counterelectrophoresis (greater than or equal to 400 ng/ml), correlated well with the presence of active disease (p less than 0.001 by Fisher's exact 2 X 2 test). A longitudinal study of serum ferritin levels in 34 of the 58 patients showed the same association of elevated serum ferritin with active disease; a return of ferritin levels to the normal ranges coincided with remission. Primary neuroblastoma tumors and cells from neuroblastoma cell lines contained ferritins with the electrophoretic characteristics different from normal liver ferritin. Supernatant fluids from six neuroblastoma cell lines grown in culture also contained ferritin. These findings suggest that the increased ferritin in the serum of patients is derived from the tumor. The serum ferritin level could be used as indicator of disease activity and as a guide to therapy.