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OBJECTIVE - The purpose of our study was to assess the effect of IV contrast medium administered at CT on serum creatinine in an oncologic ICU population and to determine which of the variables before CT are most associated with renal function after administration of contrast material.
MATERIALS AND METHODS - We retrospectively reviewed 3,848 patient admissions to an oncology ICU. The following matched comparisons were undertaken: contrast-enhanced CT versus unenhanced CT and CT (with or without contrast medium) versus no CT. Matching criteria included age, sex, baseline serum creatinine, and severity of illness (modified sequential organ failure assessment [mSOFA] score). No patients with creatinine > 2.0 mg/dL received contrast material. Groups were compared using a rank sum test. Factors influencing creatinine after administration of contrast material were evaluated by multiple regression analysis. Parallel analyses using estimated glomerular filtration rate (eGFR) also were performed.
RESULTS - No significant difference was found in absolute change in creatinine between matched contrast-enhanced CT and unenhanced CT groups (n = 81), with mean (95% CI) creatinine rises after CT of 0.25 (0.04-0.46) and 0.11 (0.04-0.18) mg/dL, respectively. Similarly, for matched CT versus non-CT groups (n = 152), mean creatinine rises were 0.15 (0.05-0.25) and 0.12 (0.08-0.16) mg/dL, respectively. Parallel analyses using eGFR yielded similar results. Creatinine after administration of contrast material was associated with sex and mSOFA (p = 0.04 and 0.02, respectively) but not baseline creatinine. eGFR after administration of contrast material was associated with baseline eGFR (p < 0.0001).
CONCLUSION - Administration of IV contrast medium in oncologic ICU patients with relatively normal creatinine is associated with an increase in creatinine but not beyond that of simply undergoing CT or of a matched non-CT group in ICU. The eGFR, which includes sex in its derivation, may be a better predictor of contrast-enhanced renal function than creatinine.
By interacting with the cytoplasmic tail of a Golgi-processed form of transforming growth factor-alpha (TGFalpha), Naked2 coats TGFalpha-containing exocytic vesicles and directs them to the basolateral corner of polarized epithelial cells where the vesicles dock and fuse in a Naked2 myristoylation-dependent manner. These TGFalpha-containing Naked2-associated vesicles are not directed to the subapical Sec6/8 exocyst complex as has been reported for other basolateral cargo, and thus they appear to represent a distinct set of basolaterally targeted vesicles. To identify constituents of these vesicles, we exploited our finding that myristoylation-deficient Naked2 G2A vesicles are unable to fuse at the plasma membrane. Isolation of a population of myristoylation-deficient, green fluorescent protein-tagged G2A Naked2-associated vesicles was achieved by biochemical enrichment followed by flow cytometric fluorescence-activated vesicle sorting. The protein content of these plasma membrane de-enriched, flow-sorted fluorescent G2A Naked2 vesicles was determined by LC/LC-MS/MS analysis. Three independent isolations were performed, and 389 proteins were found in all three sets of G2A Naked2 vesicles. Rab10 and myosin IIA were identified as core machinery, and Na(+)/K(+)-ATPase alpha1 was identified as an additional cargo within these vesicles. As an initial validation step, we confirmed their presence and that of three additional proteins tested (annexin A1, annexin A2, and IQGAP1) in wild-type Naked2 vesicles. To our knowledge, this is the first large scale protein characterization of a population of basolaterally targeted exocytic vesicles and supports the use of fluorescence-activated vesicle sorting as a useful tool for isolation of cellular organelles for comprehensive proteomics analysis.
UNLABELLED - The ability to estimate absorbed doses in experimental animals to which radiolabeled material has been administered may be important in explaining and controlling potential radiation toxicity observed during preclinical trials. Most previously reported models for establishing doses to small animals have been stylized and mathematically based. This study establishes dose factors for internal sources in realistic models of a typical mouse and a typical rat, based on image data obtained using a dedicated small-animal CT scanner.
METHODS - A transgenic mouse (body mass, 27 g) and a Sprague-Dawley rat (body mass, 248 g) were imaged using the dedicated small-animal CT scanner. Identified organs were segmented using computer tools that Vanderbilt University applies to process human images for 3-dimensional dosimetry. Monte Carlo N-particle transport code (MCNP) input files were prepared from the 3-dimensional, voxel-based image data. Using methods established for human studies, radiation transport calculations of absorbed fractions (AFs) were performed using MCNP, version 4C, on the segmented images, and dose conversion factors for several radionuclides were developed.
RESULTS - AFs were established at discrete energies for electron and photon sources assumed to be uniformly distributed throughout approximately 10 source and target regions in both models. Electron self-irradiation AFs were significantly less than 1.0 for many organs, at energies above 0.5 MeV, and significant cross irradiation was observed for high-energy electrons, such as those from (90)Y or (188)Re, in many organs. Calculated dose conversion factors reflected these trends and agreed well with the results of other authors who have undertaken similar investigations.
CONCLUSION - The AFs calculated in this study will be useful in determining the dose to organs for mice and rats similar in size to those studied here. The segmented, voxel-based models developed here can be used for external dose calculations as well.
The coronavirus replicase gene (gene 1) is translated into two co-amino-terminal polyproteins that are proteolytically processed to yield more than 15 mature proteins. Several gene 1 proteins have been shown to localize at sites of viral RNA synthesis in the infected cell cytoplasm, notably on late endosomes at early times of infection. However, both immunofluorescence and electron microscopic studies have also detected gene 1 proteins at sites distinct from the putative sites of viral RNA synthesis or virus assembly. In this study, mouse hepatitis virus (MHV)-infected cells were fractionated and analyzed to determine if gene 1 proteins segregated to more than one membrane population. Following differential centrifugation of lysates of MHV-infected DBT cells, gene 1 proteins as well as the structural N and M proteins were detected almost exclusively in a high-speed small membrane pellet. Following fractionation of the small membrane pellet on an iodixanol density gradient, the gene 1 proteins p28 and helicase cofractionated with dense membranes (1.12 to 1.13 g/ml) that also contained peak concentrations of N. In contrast, p65 and p1a-22 were detected in a distinct population of less dense membranes (1.05 to 1.09 g/ml). Viral RNA was detected in membrane fractions containing helicase, p28, and N but not in the fractions containing p65 and p1a-22. LAMP-1, a marker for late endosomes and lysosomes, was detected in both membrane populations. These results demonstrate that multiple gene 1 proteins segregate into two biochemically distinct but tightly associated membrane populations and that only one of these populations appears to be a site for viral RNA synthesis. The results further suggest that p28 is a component of the viral replication complex whereas the gene 1 proteins p1a-22 and p65 may serve roles during infection that are distinct from viral RNA transcription or replication.