Anabolic implants alter abundance of mRNA involved in muscle growth, metabolism, and inflammation in the longissimus of Angus steers in the feedlot.

The majority of beef cattle in the United States often receive at least one anabolic implant resulting in improved growth, feed efficiency, and environmental and economic sustainability. However, the physiological and molecular mechanisms through which anabolic implants increase skeletal muscle growth of beef cattle remain elusive. The objective of this study was to identify transcriptional changes occurring in skeletal muscle of steers receiving anabolic implants containing different steroid hormones. Forty-eight steers were stratified by weight into 1 of 4 (n = 12/treatment) implant treatment groups: (1) estradiol (ImpE2; 25.7 mg E2; Compudose, Elanco Animal Health, Greenfield, IN), (2) trenbolone acetate (ImpTBA; 200 mg TBA; Finaplix-H, Merck Animal Health, Madison, NJ), (3) combination (ImpETBA; 120 mg TBA + 24 mg E2; Revalor-S, Merck Animal Health), or (4) no implant (CON). Skeletal muscle biopsies were taken from the longissimus 2 and 10 d post-implantation. The mRNA abundance of 94 genes associated with skeletal muscle growth was examined. At 10 d post-implantation, steers receiving ImpETBA had greater (P = 0.02) myoblast differentiation factor 1 transcript abundance than CON. Citrate synthase abundance was increased (P = 0.04) in ImpETBA steers compared to CON steers. In ImpE2 steers 10 d post-implantation, muscle RING finger protein 1 decreased (P = 0.05) compared to CON steers, and forkhead box protein O4 decreased (P = 0.05) in ImpETBA steers compared to CON steers. Interleukin-6 abundance tended to be increased (P = 0.09) in ImpE2 steers compared to both ImpETBA and CON steers. Furthermore, interleukin-10 mRNA abundance tended to be increased (P = 0.06) in ImpTBA steers compared to ImpETBA steers. Leptin receptor abundance was reduced (P = 0.01) in both ImpE2 and ImpTBA steers when compared to CON steers. Abundance of phosphodiesterase 4B was increased (P = 0.04) in ImpTBA steers compared to CON steers 2 d post-implantation. Taken together, the results of this research demonstrate that estradiol increases skeletal muscle growth via pathways related to nutrient partitioning and mitochondria function, while trenbolone acetate improves steer skeletal muscle growth via pathways related to muscle growth.

Projective imaging of pulsatile flow with magnetic resonance.

Noninvasive angiography with magnetic resonance is demonstrated. Signal arising in all structures except vessels that carry pulsatile flow is eliminated by means of velocity-dependent phase contrast, electrocardiographic gating, and image subtraction. Background structures become in effect transparent, enabling the three-dimensional vascular tree to be imaged by projection to a two-dimensional image plane. Image acquisition and processing are accomplished with entirely conventional two-dimensional Fourier transform magnetic resonance imaging techniques. When imaged at 0.6 tesla, vessels 1 to 2 millimeters in diameter are routinely detected in a 50-centimeter field of view with data acquisition times less than 15 minutes. Studies of normal and pathologic anatomy are illustrated in human subjects.

Functional mapping of the human visual cortex by magnetic resonance imaging.

Knowledge of regional cerebral hemodynamics has widespread application for both physiological research and clinical assessment because of the well-established interrelation between physiological function, energy metabolism, and localized blood supply. A magnetic resonance technique was developed for quantitative imaging of cerebral hemodynamics, allowing for measurement of regional cerebral blood volume during resting and activated cognitive states. This technique was used to generate the first functional magnetic resonance maps of human task activation, by using a visual stimulus paradigm. During photic stimulation, localized increases in blood volume (32 +/- 10 percent, n = 7 subjects) were detected in the primary visual cortex. Center-of-mass coordinates and linear extents of brain activation within the plane of the calcarine fissure are reported.

Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging.

The borders of human visual areas V1, V2, VP, V3, and V4 were precisely and noninvasively determined. Functional magnetic resonance images were recorded during phase-encoded retinal stimulation. This volume data set was then sampled with a cortical surface reconstruction, making it possible to calculate the local visual field sign (mirror image versus non-mirror image representation). This method automatically and objectively outlines area borders because adjacent areas often have the opposite field sign. Cortical magnification factor curves for striate and extrastriate cortical areas were determined, which showed that human visual areas have a greater emphasis on the center-of-gaze than their counterparts in monkeys. Retinotopically organized visual areas in humans extend anteriorly to overlap several areas previously shown to be activated by written words.

Associations of Arthritis-Attributable Interference with Routine Life Activities: A Modifiable Source of Compromised Quality-of-Life.

OBJECTIVE: Arthritis patients experience the impact of disease beyond routinely assessed clinical measures. We characterized arthritis-attributable interference in four important routine life domains: 1) recreation/leisure/hobbies; 2) household chores; 3) errands/shopping; and 4) social activities. METHODS: Participants were from the Arthritis Conditions Health Effects Survey (2005-2006), a cross-sectional survey of noninstitutionalized US adults 45 years or older with doctor-diagnosed arthritis (n = 1793). We estimated the prevalence of "a lot" of arthritis-attributable interference and quantified the associations between sociodemographic, clinical, and psychological characteristics and "a lot" of arthritis-attributable interference (vs "a little" or "none") in each domain using prevalence ratios (PRs) in multivariable (MV)-adjusted logistic regression models. RESULTS: An estimated 1 in 5 to 1 in 4 adults with arthritis reported "a lot" of arthritis-attributable interference in recreation/leisure/hobbies (27%), household chores (25%), errands/shopping (22%), and social activities (18%). The highest prevalence of "a lot" of arthritis-attributable interference was for those unable to work/disabled or reporting severe arthritis symptoms (pain, stiffness, fatigue), anxiety, depression, or no/low confidence in ability to manage arthritis, across domains. In MV-adjusted models, those unable to work/disabled, currently seeing a doctor, or reporting fair/poor self-rated health, severe joint pain, anxiety, or no/low confidence in ability to manage arthritis were more likely to report arthritis-attributable interference than their respective counterparts. Magnitudes varied by domain but were consistently strongest for those unable to work/disabled (MV PR range = 1.8-2.5) and with fair/poor health (MV PR range = 1.7-2.7). CONCLUSION: Many characteristics associated with arthritis-attributable interference in routine life activities are potentially modifiable, suggesting unmet need for use of existing evidence-based interventions that address these characteristics and reduce interferences to improve quality of life.

Trapping of dextran-coated colloids in liposomes by transient binding to aminophospholipid: preparation of ferrosomes.

A procedure is described that allows to increase the efficiency of the loading of liposomes with dextran-stabilized iron oxides (MION). The method produces a preparation of liposomes (REVs) with high iron oxide content as a result of transient binding of oxidized dextran with amino groups of aminophospholipids. Phosphatidylethanolamine (PE)-containing lipid mixtures (PC/DOPE/CH or SM/DOPE/CH, 9:2:9 molar ratio) in organic phase were combined with oxidized MION at pH 8. Liposomes then were obtained by reversed-phase evaporation. Liposomes, 263 +/- 89 nm in diameter, contained up to 11.8 mol Fe/mol phospholipid (encapsulation yield 49%). 10.2% of liposome-associated iron was dissociated from liposomes upon changing the pH to 4.5. When lipid compositions of extracts prepared from liposomes incubated at pH 4.5 and pH 8.0 were compared, an increase of relative PE-content in extracts of liposomes incubated at lowered pH was detected. This indicates a dissociation of imine bonds between aldehydes on the MION surface and PE. The accessibility of liposomal PE for acylation was demonstrated by modification with an activated ester of methoxy poly(ethylene glycol) succinate. Control liposomes, containing no aminophospholipid, or PE-containing liposomes obtained in the presence of non-oxidized MION, were 3.5-5-fold less effective for MION encapsulation and showed extensive aggregation.

The fluorinated anesthetic halothane as a potential NMR biologic probe.

Fluorinated anesthetics such as halothane preferentially partition into hydrophobic environments such as cell membranes. The 19F-NMR spectrum of halothane in a rat adenocarcinoma (with known altered lipid metabolism and membrane composition) shows an altered chemical shift pattern compared to the anesthetic in normal tissue. In eight tumor samples examined, the 19F-NMR spectra exhibit two distinct resonances, compared to a single resonance observed in normal tissues. This is explained by an enhanced or altered hydrophobic component in the tumor tissue giving rise to two discrete halothane environments. Another fluorinated anesthetic, isoflurane, shows similar behavior in distinguishing normal from diseased tissue. Given the large chemical shift range of fluorine and the inherent sensitivity of this nucleus, 19F-NMR spectra of fluorinated anesthetics can also be used to follow anesthetic degradation by the liver. The ability of fluorinated anesthetics to discriminate tissues and to monitor metabolic processes is potentially useful for in vivo 19F-NMR surface coil and imaging studies.

In vivo detection of reperfused myocardium by nuclear magnetic resonance imaging.

To assess the potential of in vivo nuclear magnetic resonance imaging for the detection of reperfused myocardium, in vivo T2-weighted spin echo images were obtained of dogs at 0.15 tesla. Imaging was done during 3 hours of coronary occlusion (group I), and during 3 hours of coronary occlusion followed by 1 hour of reperfusion (group II). On sacrifice, the hearts were drained of blood and imaged in situ to determine the effect of in vivo imaging on myocardial signal intensity. The hearts were then excised and imaged at 1.4 tesla to compare the effect of high resolution imaging on image quality. Of the six hearts in group I and the eight hearts in group II with a myocardial infarction and suitable image quality, four of the former hearts and six of the latter demonstrated a small but visible increase in infarct signal intensity at 3 hours of occlusion on the time to echo [TE] = 60 ms, single echo images. The T2 (transverse) relaxation time of the infarct (measured in vitro by spectrometer) increased by 13% when compared with normal tissue. In contrast, the reperfused infarct was more easily visualized, with signal intensity increasing by 31 +/- 17% and infarct T2 increasing by 20%. Imaged at 1.4 tesla, the excised hearts showed the infarct to be subendocardial during occlusion and extending transmurally with reperfusion. It is concluded that, although visualized, the increase in infarct signal intensity at 3 hours of coronary occlusion is small and this is consistent with the small increase in infarct signal intensity and T2 relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive tissue characterization: diagnosis of lipomatous hypertrophy of the atrial septum by nuclear magnetic resonance imaging.

An atrial septal mass was identified by echocardiogram in a patient with multiple subcutaneous lipomas. In order to differentiate the benign condition of lipomatous hypertrophy from myxoma, thrombus and other tumors, nuclear magnetic resonance and computed tomographic imaging were performed. Both techniques identified the adipose nature of the tissue noninvasively, consistent with the diagnosis of lipomatous hypertrophy. Pathologically demonstrated lipomatous hypertrophy in a postmortem heart was similarly characterized by nuclear magnetic resonance imaging.

Comparison of magnetic resonance and roentgen ray computed tomography in dementia.

To compare the merits of magnetic resonance imaging (MRI) and roentgen ray computed tomography (CT) in assessing patients with dementia, we examined pairs of MR and CT brain images obtained from 26 patients with Alzheimer's disease (AD), eight patients with vascular or mixed dementia, and two patients with Parkinson's disease plus dementia. Magnetic resonance and CT images were independently rated on a qualitative scale of 0 (normal) to 3 (severely abnormal) in 39 separate brain regions. Ratios of anterolateral and third ventricular linear spans to linear skull spans were measured. Abnormalities in subcortical white matter and in hippocampus, enlargement of basal and sylvian cisterns, and ventriculomegaly were more evident on MR than CT scans, but qualitative ratings in all other brain regions were similar. Linear ventricular span ratios based on MR images did not differ significantly from those measured on CT. White matter abnormalities on MR were high signal foci on T2-weighted images whose pathologic substrate was uncertain; in a single case studied pathologically, no abnormalities were detected in brain regions that contained high signal foci. Dementia severity correlated with periventricular white matter abnormalities on both MR and CT images.

Central pontine myelinolysis: demonstration by nuclear magnetic resonance.

An alcoholic, hyponatremic woman developed central pontine myelinolysis (CPM) and improved from a decerebrate, comatose state to alertness and full ambulation. NMR, using inversion-recovery and spin-echo pulse sequences, was performed sequentially from 4 weeks to 8 months after onset of symptoms and revealed a well-defined lesion with prolonged relaxation times. The lesion was anatomically consistent with CPM and was initially also visualized by CT. NMR showed no definite temporal change in the qualitative appearance of the lesion until the 8-month scan; however, quantitatively, a reduction of relaxation times was noted with each serial study.

Relationship of changes in pH and energy status to hypoxic cell fraction and hyperthermia sensitivity.

The relative concentrations of nucleotide triphosphates, creatine phosphate, inorganic phosphate, and pH have been evaluated as a function of tumor volume in a murine fibrosarcoma (FSaII) by 31P NMR spectroscopy. As the tumor volume increased from 60-1250 mm3, the ratio of phosphocreatine to inorganic phosphate systemically decreased. This decrease paralleled a decrease in the ratio of nucleotide triphosphate to inorganic phosphate in the same tumor volume range. The tumor pH as measured by 31P NMR decreased slightly with tumor growth. A pH of 7.17 +/- 0.07 (n = 17) was found for tumors between 60 and 150 mm3, whereas for tumors greater than 900 mm3, a pH of 7.05 +/- .03 (n = 6) was noted. Intermediate size tumors (151-900) had a pH of 7.12 +/- 0.09 (n = 18). The change in tumor energy status with tumor volume inversely paralleled the change in tumor radiobiologic hypoxic cell fraction and suggested a causal relationship between tumor nutrient status and energy status. Tumor thermal sensitivity also increased with tumor volume, suggesting a relationship between pH, energy status, and thermal sensitivity, as has been demonstrated under in vitro conditions. Each NMR parameter was found to correlate significantly with tumor volume independent of the other NMR parameters.

The importance of adequate exercise in the detection of coronary heart disease by radionuclide ventriculography.

Rest and exercise radionuclide ventriculograms were obtained on 77 symptomatic patients without prior documented coronary artery disease (CAD). Coronary artery disease was present by angiograms in 48. Radionuclide ventriculography (RNV) was abnormal in 41 patients (overall sensitivity 85%). In 29 patients with normal coronary arteries, RNV was normal in 24 (specificity 83%). To determine if the exercise level affects sensitivity, the studies were graded for adequacy of exercise. It was considered adequate if patients developed (a) chest pain, or (b) ST segment depression of at least 1 mm, or (c) if they achieved a pressure rate produce greater than 250. Among the 48 patients with coronary artery disease, 35 achieved adequate exercise. Thirty-three had an abnormal RNV (sensitivity 94%). In 13 patients who failed to achieve adequate exercise, RNV was abnormal in eight (sensitivity of only 62%). Some patients with coronary artery disease may have a normal ventricular response at inadequate levels of stress.

Cardiac function in patients with prior myocarditis.

Gated cardiac blood-pool imaging under rest and exercise was used to assess left-ventricular functional reserve in six asymptomatic patients with prior myocarditis and six age matched control subjects. Coronary artery disease was excluded in three of the six patients by coronary arteriography. In the remaining three, coronary artery disease was thought unlikely on the basis of history and the presence, during exercise, of a normal ECG and normal Tl-201 myocardial image. Conventional indices of resting left-ventricular function--including cardiothoracic ratio, echocardiographic left-ventricular diameter, and percentage change in minor diameter--were normal in those with prior myocarditis. The mean resting left-ventricular ejection fraction was also normal by gated blood-pool imaging, and not significantly different from that for control patients: 0.58 +/- 0.05 and 0.65 +/- 0.02, respectively. Three patients with prior myocarditis had resting left-ventricular ejection fractions of less than 0.50. On exercise, the patients with prior myocarditis decreased their mean left-ventricular ejection fraction by an average of 8% compared with an increase of 15% in the control group (p less than 0.01). This study suggests that asymptomatic patients with prior myocarditis have left-ventricular dysfunction that may not be clinically apparent, and suggests the need for further long-term follow-up.

Gallium-67 and magnetic resonance imaging in aortic root abscess.

Perivascular abscess in the aortic root is a serious complication of infective endocarditis and is recognized infrequently with noninvasive techniques. This report describes a patient with sepsis who was imaged with 67Ga and magnetic resonance (MR) in order to locate a site of infection. The 67Ga image showed increased activity in the substernal region. Magnetic resonance correctly detected the multilocular aortic root abscess, which had extended into the interatrial septum. The combination of the sensitive 67Ga with the high-resolution MR image provided a useful method to locate aortic root abscesses and to identify contiguous spread.

Contrast agents and spectroscopic probes in NMR.

The demand for higher diagnostic specificity has led to the increased use of "foreign" agents to increase tissue contrast and/or spectroscopic sensitivity in NMR studies. The primary agents used to enhance tissue contrast in NMR imaging are paramagnetic. They cause a decrease in the proton T1 of H2O leading to enhanced signal intensity. This effect depends on the large gyromagnetic ratio of the electron, the number of unpaired electrons, the concentration of paramagnetic ions, the number of coordinated water molecules, and the rate of exchange of water. Spectroscopic enhancement has relied primarily on attempt at isotopic enrichment (usually C-13), which causes a direct increase in signal.

Coded-aperture imaging of the heart.

Coded-aperture imaging of the heart combines the advantages of tomography with good sensitivity, high resolution, and accurate size scaling. Since the images are multiplexed, the method may be adapted to small, portable cameras for bed-side use without sacrificing image resolution. A new coded aperture designed especially for cardiac imaging has been constructed and tested. This aperture incorporates significant improvements over previous designs. Longitudinal tomograms are calculated at 1-cm intervals using a modified ART algorithm. Experimental lateral resulution at 140 keV with a portable scintillation camera is 3.8 mm FWHM at 4 cm, and 7.8 mm FWHM at 12 cm. Dpth resolution determined from a sloping line source is 1.1 cm FWHM at 4 cm, and 2.9 cm at 12 cm. The calculated point-source sensitivities in air at 4 cm and 12 cm, respectively, are 20 and 8 cps/microCi. Images of good diagnostic quality have been obtained in phantoms and in a dog model of acute myocardial infarction, using thallium-201, technetium-99m pyrophosphate, and gated ventricular blood-pool imaging with Tc-labeled red blood cells. Preliminary studies in humans confirm the good results in animals.

Synthetic copolymer kit for radionuclide blood-pool imaging.

UNLABELLED: A synthetic blood pool imaging agent labeled with 99mTc is reported. METHODS: The agent, methoxypolyethylene glycol-poly-L-lysyl-diethylenetriaminepentaacetate monoamide was synthesized from a covalent graft copolymer of methoxypolyethylene glycol succinate (molecular weight 5.1 kD) and poly-L-lysine (molecular weight average 35.6 kD) with subsequent modification of the product with diethylenetriamineacetyl residues. The polymer was formulated into a kit that contained Sn(II) and sodium acetate for radiolabeling with 99mTc. Biodistribution studies were performed in rats. Blood-pool imaging and blood clearance determination was carried out in rabbits and in a rhesus monkey. RESULTS: The 99mTc-labeled agent [specific activity greater than 3.7 GBq/mg; radiochemical purity more than 98% by thin-layer and high-performance liquid chromatography (HPLC)] demonstrated remarkable stability in solution (pH 5.5-6.5) with no radioactive products of degradation detectable by HPLC even at 24 hr postlabeling. The agent exhibited prolonged circulation in the blood with a half-life of 31.5 hr in rabbits. Biodistribution in rats showed a lack of substantial accumulation of the agent in the reticuloendothelial system. Sequential acquisitions were performed in a rhesus monkey. The 99mTc-labeled polymer kit was compared with the 99mTc-red blood cells (RBCs) labeled in vitro. Both methods produced similar heart-to-lung ratios. The ratios remained essentially unchanged for up to 15 hr postinjection. CONCLUSION: The 99mTc-labeled methoxypolyethylene glycol-poly-L-lysyl-diethylenetriamine pentaacetate monoamide is an attractive alternative to radiolabeled RBCs for blood pool imaging applications.

Use of gadolinium-DTPA as a myocardial perfusion agent: potential applications and limitations for magnetic resonance imaging.

To establish the effect of the paramagnetic contrast agent gadolinium diethylenetriaminepentaacetic acid ([Gd]DTPA) on myocardial magnetic resonance relaxation parameters T1 and T2, and its relationship to myocardial perfusion, we administered [Gd] DTPA 0.2 mM/kg to two groups of dogs. Group I had severe, resting myocardial ischemia induced by coronary occlusion, followed in 2 min by [Gd]DTPA infusion and heart excision 1 min later. Group II had a variable reduction in blood flow. In Group II the coronary vasodilator dipyridamole was infused to enhance blood flow to the normal myocardium before [Gd]DTPA was given. In Group I [Gd]DTPA caused a significant difference in T1 between the normal and severely ischemic zones; changes in T1 correlated with the severity of myocardial ischemia. Although vasodilatation delivered more Gd-DTPA to the normal myocardium in Group II, the lack of further decrease in T1 suggested that it was cleared more rapidly. Thus, [Gd]DTPA permits the detection and characterization of severe, resting myocardial ischemia by magnetic resonance techniques. Using the experimental techniques described in this study, less severe flow differences caused by vasodilatation and resultant hyperemia are not detected.

Calculation of viable and infarcted myocardial mass from thallium-201 tomograms.

The feasibility of determining the mass of both viable and infarcted myocardium from tomographic images of thallium-201 distribution in the heart was studied in two normal dogs and ten dogs with acute infarction. Twenty-four hours after occlusion, thallium-201 was injected and 10 min later the hearts were removed and transaxial emission computed tomograms were obtained. Using the computer, an operator defined the epi- and endocardial surfaces of the left ventricle and the area of infarction in each tomogram. The computer then calculated values for total left-ventricular mass (TLVM) infarcted mass (IM) and the percentage of the left ventricle infarcted (% LVI). The calculated values were compared with measured weights, and good correlation was found between them: for TLVM, r = 0.87; for IM, r = 0.90; and for %LVI, r = 0.87. Good interobserver and intra-observer correlations were also found. Thallium-201 emission computed tomography offers a potential means to measure both myocardial mass and acute myocardial injury.