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C S Hall

Publications and source records attributed to C S Hall.

At least 19 recordsLinked to original sources
PubMed2002

Solvated electrons in very small clusters of polar molecules: (HF)(3)(-).

Photoelectron spectra of (HF)(3)(-) reveal coexistence of two anionic isomers with vertical electron detachment energies (VDE) of 0.24 and 0.43 eV. The results of electronic-structure calculations, performed at the coupled cluster level of theory with single, double, and noniterative triple excitations, suggest that the two isomers observed experimentally are an open, zigzag, dipole-bound anion and an asymmetric solvated electron, in which the dipole-bound anion of (HF)(2) is solvated by one HF monomer at the side of the excess electron. The theoretical VDE of 0.21 and 0.44 eV, respectively, are in excellent agreement with the experimental data.

Journal Article↗
PubMed2001

FK506 promotes adenosine release from endothelial cells via inhibition of adenosine kinase.

The immunosuppressants, cyclosporin A and tacrolimus (FK506) induce an increase in plasma levels of adenosine and mimic ischemic preconditioning. However, the mechanism of action of the two drugs on adenosine metabolism is not clear. Since inhibition of adenosine kinase promotes an increase in endogenous adenosine release, we tested a hypothesis that FK506 induces adenosine release via inhibition of adenosine kinase activity. In cultured endothelial cells, FK506 enhanced release of tracer adenosine and inhibited uptake of tracer adenosine. It also reduced adenosine kinase activity of the cell membrane fraction. In addition, FK506 does not inhibit membrane transport of tracer adenosine. These observations indicate that FK506 inhibits in situ adenosine kinase activity in endothelial cells. Other cell signaling inhibitors were found to inhibit adenosine uptake via inhibition of adenosine transport. In conclusion, FK506 promotes adenosine release from endothelial cells by a novel mechanism involving inhibition of adenosine kinase activity associated with the membrane.

Adenosine↗
PubMed2001

Cellular and molecular actions of adrenomedullin in glomerular mesangial cells.

Adrenomedullin (AM), a potent vasodilatory and hypotensive peptide produces several biological outcomes in glomerular mesangial cells. Mesangial cells are important in the pathogenesis of glomerulonephritis, and therefore the actions of AM on mesangial cells have important clinical and therapeutic implications. This minireview describes the various actions of AM on mesangial cell function and the signal transduction mechanisms involved. As in other systems, most actions of AM can be explained by increase in cAMP levels in the cell, although a few exceptions remain. The fact that most data obtained to date has been in culture, the physiological significance of the actions of AM in mesangial cells is discussed.

Adrenomedullin↗
PubMed2001

Age-related alterations of cardiac tissue microstructure and material properties in Fischer 344 rats.

The cardiac aging process is accompanied by global mechanical dysfunction that reflects increased myocardial stiffness. Accordingly, age-related changes in microscopic material properties of myocardium were delineated with high-frequency ultrasound (US) (30 to 44 MHz) tissue characterization methods for aging Fischer 344 rats at 6 (adult), 18 (aged), and 24 (senescent) months of age. The excised lateral wall of the left ventricle of rats (n = 10 per group) was insonified with a 50-MHz acoustic microscope for determination of integrated backscatter, backscatter coefficient and attenuation coefficient. Histological and biochemical analyses for collagen content and cardiac myocyte diameter were performed. Collagen concentration increased progressively with age, with the greatest increments occurring from 6 to 18 months (38.0 +/- 6.3 to 53.0 +/- 7.1 mg/g dry wt), and leveling off at 24 months (60.0 +/- 7.4 mg/g dry wt). Tissue microscopic material properties also changed progressively from 6 to 24 months of age, as determined by US methods: integrated backscatter increased (-44.7 +/- 1.8 vs. -40.8 +/- 1.9 dB, p < 0.05), attenuation increased (47.1 +/- 5.9 to 65.3 +/- 7.8 dB/cm, p < 0.05), and the backscatter coefficient increased (0.73 +/- 0.16 x 10(-5) to 3.76 +/- 1.6 x 10(-5) cm(-1), p < 0.05), from 6 to 24 months of age in each case. Age-related alterations in indices of cardiac microscopic material properties were closely correlated with the changes in cardiac microstructure. Ultrasonic tissue characterization may prove to be a sensitive tool to monitor changes in the cardiac microstructure, such as increased collagen deposition, that occur within age-related diastolic dysfunction.

Aging↗
PubMed2001

Temperature dependence of ultrasonic enhancement with a site-targeted contrast agent.

Molecular imaging contrast agents specifically detect the biochemical "signatures" of disease before anatomical manifestations are apparent. Sensitive and specific localization of fibrin both in vivo and in vitro has been demonstrated with the use of a ligand-directed liquid perfluorocarbon nanoparticle. Since the acoustic properties of perfluorocarbons are known to vary with temperature, it was hypothesized that temperature could be used to augment the magnitude of enhancement imparted by targeted nanoparticles. Accordingly, the acoustic backscatter of two different substrates, nitrocellulose membrane and human plasma clot, targeted by the nanoparticles was measured at temperatures ranging from 27 degrees to 47 degrees C in 5 degrees C increments. Classic avidin-biotin interactions were utilized to couple biotinylated nanoparticles to avidin-conjugated nitrocellulose membranes. Ultrasonic contrast enhancement of the nitrocellulose membrane at 25 MHz, measured by acoustic microscopy, increased from 2.0+/-0.3 dB at 27 degrees C to 3.7+/-0.4 at 47 degrees C. In a similar experiment, antifibrin nanoparticles bound to human plasma clots also exhibited temperature-dependent ultrasonic signal enhancement ranging from 13.9+/-1.5 dB at 27 degrees C to 18.1+/-1.5 dB at 47 degrees C. The increase in ultrasonic contrast enhancement measured was well described by a simple, acoustic transmission line model with temperature-dependent impedance. These results suggest that temperature-dependent changes in acoustic backscatter may be used to further differentiate tissues targeted with site-specific nanoparticles from surrounding normal soft tissues.

Acoustics↗
PubMed2000

Adrenomedullin decreases extracellular signal-regulated kinase activity through an increase in protein phosphatase-2A activity in mesangial cells.

Adrenomedullin is a recently identified peptide hormone that has receptors in a number of different systems including renal mesangial cells. We reported recently that adrenomedullin can cause a decrease in extracellular signal-regulated kinase (ERK) activity and increase jun amino-terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38 MAPK) acitivities in rat mesangial cells. Associated with these responses we also reported that adrenomedullin can decrease proliferation and increase apoptosis in mesangial cells. The major aim of the present study was to examine the mechanism of decrease in ERK activity by adrenomedullin and to identify the role of protein phosphatase 2A (PP2A) in the decrease in ERK activity, using okadaic acid [9,10-Deepithio-9,10-didehydroacanthifolicin], a selective inhibitor of PP2A at low nanomolar concentrations. The adrenomedullin-induced decrease in [3H]-thymidine incorporation and increase in apoptosis were reversed by okadaic acid at the concentration that selectively inhibits PP2A. Okadaic acid completely reversed the ERK inhibition caused by adrenomedullin, suggesting that PP2A may be involved in the adrenomedullin-mediated changes in proliferation, apoptosis and ERK activity. PP2A activity in mesangial cells was increased over time following exposure to adrenomedullin. The tyrosine phosphorylation of ERK did not change significantly following adrenomedullin treatment although the ERK activity was decreased significantly. This suggests that the decrease in ERK activity is not mediated through a decrease in MEK (a dual phosphorylating kinase upstream of ERK) or by an increase in MKP-1/2 (a dual specificity phosphatase) activities. Thus we conclude that the mechanism of adrenomedullin-induced decrease in ERK activity in rat mesangial cells is at least in part mediated by an increase in PP2A activity.

Adrenomedullin↗
PubMed2000

High-resolution MRI characterization of human thrombus using a novel fibrin-targeted paramagnetic nanoparticle contrast agent.

In this study, the sensitivity of a novel fibrin-targeted contrast agent for fibrin detection was defined in vitro on human thrombus. The contrast agent was a lipid-encapsulated perfluorocarbon nanoparticle with numerous Gd-DTPA complexes incorporated into the outer surface. After binding to fibrin clots, scanning electron microscopy of treated clots revealed dense accumulation of nanoparticles on the clot surfaces. Fibrin clots with sizes ranging from 0.5-7.0 mm were imaged at 4.7 T with or without treatment with the targeted contrast agent. Regardless of sizes, untreated clots were not detectable by T(1)-weighted MRI, while targeted contrast agent dramatically improved the detectability of all clots. Decreases in T(1) and T(2) relaxation times (20-40%) were measured relative to the surrounding media and the control clots. These results suggest the potential for sensitive and specific detection of microthrombi that form on the intimal surfaces of unstable atherosclerotic plaque.

Antibodies, Monoclonal↗
PubMed2000

High-frequency ultrasound for quantitative characterization of myocardial edema.

Myocardial edema has been associated with impaired ventricular compliance and diastolic filling. To determine the sensitivity of high-frequency (40 MHz) ultrasound to myocardial edema, we employed a model in which myocardial edema was induced by immersion of tissue in isotonic saline. The effect of freezing tissue on edema formation was also evaluated. Rat hearts were arrested at end-diastole and insonified fresh within 15 min of excision (n = 5) or following being frozen for 24 h and thawed (n = 4). Measurements of attenuation, backscatter, tissue thickness and speed of sound were performed at baseline and hourly for 4 h, and compared with direct measurements of myocardial edema. Fresh tissue demonstrated a greater propensity for the development of edema than frozen tissue. Integrated backscatter increased in both tissues, whereas the magnitude and slope of attenuation decreased as edema evolved. We conclude that high-frequency ultrasound sensitively detects myocardial edema, and we propose that the extension of these methods to clinical frequencies may prove useful for monitoring and treatment of cardiac edematous disease states.

Acoustics↗
PubMed2000

Delineation of the extracellular determinants of ultrasonic scattering from elastic arteries.

Elastic arteries consist of three primary components: elastin fibers, extracellular collagen matrix and smooth muscle cells. However, the relative contribution of elastin and collagen fibers to overall ultrasonic scattering from an intact arterial wall is poorly understood. To define the principal source of extracellular scattering from the medial layer of elastic arteries, canine ascending aortas (n = 10) were excised, fixed and sectioned for insonification. Subsequently, aortic specimens were restudied after treatment to dissolve all tissue components except extracellular collagen matrix (n = 5) and elastin fibers (n = 5). Histological staining revealed very few elastin fibers and sparse intact collagen in collagen-isolated and elastin-isolated tissues, respectively. Integrated backscatter, attenuation and backscatter coefficients differentiated these two treated tissues. The backscatter coefficient for elastin-isolated tissue demonstrated a fivefold increase over collagen-isolated tissue, suggesting that elastin fibers represent a primary scattering component within elastic arteries, and the collagen fibers may provide a secondary component of scattering.

Animals↗
PubMed2000

In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles.

Molecular imaging permits tissues to be functionally characterized by identification of specific cell-surface receptors with targeted contrast agents. In our study, a ligand-targeted acoustic nanoparticle system was used to identify the angioplasty-induced expression of tissue factor by smooth muscle cells within the tunica media. Pig carotid arteries were overstretched bilaterally with balloon catheters, treated with a tissue factor-targeted or a control nanoparticle system, and imaged with intravascular ultrasound (20 MHz) before and after treatment. Carotid wall acoustic reflectivities were unaffected by overstretch injury. Tissue factor-targeted nanoemulsion bound and increased the echogenicity of smooth muscle cells expressing tissue factor within the tunica media. The targeted emulsion increased the arterial wall gray scale (99.4+/-14.5; P<.05) relative to pretreatment (41.8+/-11.1, P<0.05) and the control gray scale (pre-emulsion: 49.3+/-9.5; post-emulsion: 43.7+/-6.4; P<.05). The area of acoustic enhancement appeared to coincide with expression of induced tissue factor in the tunica media confirmed by immunohistochemistry. We have demonstrated that this novel nanoemulsion can infiltrate into arterial walls after balloon injury and localize the expression of overstretch-induced tissue factor within pig carotid arteries. Molecular imaging and quantification of complex, biochemical change, such as tissue factor expression after angioplasty, may prove to be a prognostically important predictor of subsequent restenosis.

Acoustics↗
PubMed2000

Molecular imaging of stretch-induced tissue factor expression in carotid arteries with intravascular ultrasound.

RATIONALE AND OBJECTIVES: Molecular imaging with targeted contrast agents enables tissues to be distinguished by detecting specific cell-surface receptors. In the present study, a ligand-targeted acoustic nanoparticle system is used to identify angioplasty-induced expression of tissue factor by smooth muscle cells within carotid arteries. METHODS: Pig carotid arteries were overstretched with balloon catheters, treated with tissue factor-targeted or a control nanoparticle system, and imaged with intravascular ultrasound before and after treatment. RESULTS: Tissue factor-targeted emulsions bound and increased the echogenicity and gray-scale levels of overstretched smooth muscle cells within the tunica media, versus no change in contralateral control arteries. Expression of stretch-induced tissue factor in carotid artery media was confirmed by immunohistochemistry. CONCLUSIONS: The potential for abnormal thrombogenicity of balloon-injured arteries, as reflected by smooth muscle expression of tissue factor, was imaged using a novel, targeted, nanoparticulate ultrasonic contrast agent.

Animals↗
PubMed2000

Time evolution of enhanced ultrasonic reflection using a fibrin-targeted nanoparticulate contrast agent.

Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, unstable atherosclerotic plaques, and areas of remote thrombi. In previous studies, acoustic enhancement of blood clot morphology was demonstrated with the use of a nongaseous, fibrin-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this study, a system was designed and constructed that allows visualization of the evolution of acoustic contrast enhancement. To evaluate the system, two targets were examined: avidin-complexed nitrocellulose membrane and human plasma clots. The time evolution of enhancement was visualized in 10-min increments for 1 h. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose membranes for targeted emulsions containing perfluorooctylbromide (1.30+/-0.3 dB) and for perfluorooctane (2.64+/-0.5 dB) within the first 60 min of imaging. In comparison, the inherently nonechogenic plasma clots showed a substantial increase of 12.0+/-0.9 dB when targeted with a perfluoro-octane emulsion. This study demonstrates the concept of molecular imaging and provides the first quantifiable time-evolution report of the binding of a site-targeted ultrasonic contrast agent. Moreover, with the incorporation of specific drug treatments into the nanoparticulate contrast agent, ultrasonic molecular imaging may yield reliable detection and quantification of nascent pathologies and facilitate targeted drug therapy.

Contrast Media↗
PubMed2000

The extracellular matrix is an important source of ultrasound backscatter from myocardium.

Ultrasound tissue characterization with measurement of backscatter has been employed in numerous experimental and clinical studies of cardiac pathology, yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified. This laboratory has proposed a mathematical model for myocardial backscatter that postulates the fibrous extracellular matrix (ECM) as a significant determinant of backscatter. To demonstrate the importance of ECM, this group sought to determine whether measurements of backscatter from the isolated ECM could reproduce the known directional dependence, or anisotropy of backscatter, from intact cardiac tissues in vitro. Segments of left ventricular free wall from ten formalin fixed porcine hearts were insonified at 50 MHz, traversing the heart wall from endo- to epicardium to measure the anisotropy of myocardial backscatter, defined as the difference between peak (perpendicular to fibers) and trough (parallel to fibers) backscatter amplitude. The tissue segments were then treated with 10% NaOH to dissolve all of the cellular components, leaving only the intact ECM. Scanning electron micrographs (SEM) were obtained of tissue sections to reveal complete digestion of the cellular elements. The dimensions of the residual voids resulting from cell digestion were approximately the diameter of the intact myocytes (10-30 microm). These samples were reinsonified after seven days of treatment to compare the anisotropy of integrated backscatter. The magnitude of anisotropy of backscatter changed from 15.4 +/- 0.8 to 12.6 +/- 1.1dB for intact as compared with digested specimens. Because digestion of the myocardium leaves only extracellular sources of ultrasonic scattering, and because the isolated ECM exhibits similar ultrasonic anisotropy as does the intact myocardium, it is concluded that there is a direct association between the ECM and the anisotropy of backscatter within intact tissue. Thus, it is suggested that ultrasonic tissue characterization represents a potentially clinically applicable method for delineating the structure and function of the ECM.

Animals↗
PubMed1999

Efficacy of salvage therapy containing ritonavir and saquinavir after failure of single protease inhibitor-containing regimens.

OBJECTIVE: To assess the efficacy of salvage therapy containing ritonavir and saquinavir after failure of indinavir- or nelfinavir-containing regimens, and to determine correlates of success or failure. DESIGN: Retrospective chart review. SETTING. The Moore Clinic - the HIV clinic of Johns Hopkins Hospital. PATIENTS: Forty-one HIV-infected patients were identified through physician contacts, referrals from other providers, and review of a comprehensive clinical database. MAIN OUTCOME MEASURES: To determine response to salvage therapy, HIV-1 viral RNA (absolute and log10-transformed) was measured using the Roche Amplicor quantitative HIV-1 RNA assay after initiation of the salvage regimen. Potential correlates of response included: viral RNA at the time of switch; viral RNA at the time of switch as a percentage of baseline viral RNA; magnitude of decline in viral RNA; and the interval between virologic failure of single protease inhibitor therapy and switch to the salvage regimen. RESULTS: Thirteen (56.5%) of 23 patients failing indinavir responded to salvage therapy (HIV RNA < 400 copies/ml) with persistence throughout the follow-up period (median of 37 weeks; range 18-67 weeks). Mean absolute viral RNA at the time of switch was 20 238 copies/ml (median, 9281) compared with 42 953 copies/ml (median, 24 650) for the 10 non-responders. Mean log10 viral RNA at switch was 3.804 for responders versus 4.405 for non-responders (P = 0.040). Among four responders who had failed nelfinavir, mean viral RNA was 9634 copies/ml and mean log10 viral RNA was 3.749 at the time of switch. Two non-responders had a mean viral RNA of 21 551 and a mean log10 viral RNA of 4.037 at switch. CONCLUSIONS: In contrast with previous reports, salvage regimens containing ritonavir and/or saquinavir can be effective and durable following the failure of combination regimens containing either indinavir or nelfinavir. Salvage therapy may be more likely to succeed when it is initiated early in failure at low viral loads.

Adult↗
PubMed1998

Broadband measurements of phase velocity in Albunex suspensions.

The phase velocities in suspensions of Albunex, an ultrasound contrast agent, are determined using the technique of broadband phase spectroscopy. In these suspensions, phase velocities were measured as a function of Albunex concentration in Isoton II (buffered saline). The dispersion over the measurement bandwidth (1-15 MHz) grew with increasing Albunex concentration, exhibiting a 221-m/s change (17% increase) in phase velocity between 1.0 and 3.8 MHz at the highest concentration reported (32 microL Albunex/8 mL Isoton). The dispersion behavior of the Albunex suspensions is described using a model of encapsulated gas bubbles. The influence of the dispersion in Albunex on broadband pulses is discussed, as well as the potential impact this dispersion may have on the formation of ultrasonic images of the heart.

Albumins↗
PubMed1998

In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy.

Targeted ultrasonic contrast systems are designed to enhance the reflectivity of selected tissues in vivo [Lanza et al., Circulation 94, 3334 (1996)]. In particular, these agents hold promise for the minimally invasive diagnosis and treatment of a wide array of pathologies, most notably tumors, thromboses, and inflamed tissues. In the present study, acoustic microscopy was used to assess the efficacy of a novel, perfluorocarbon based contrast agent to enhance the inherent acoustic reflectivity of biological and synthetic substrates. Data from these experiments were used to postulate a simple model describing the observed enhancements. Frequency averaged reflectivity (30-55 MHz) was shown to increase 7.0 +/- 1.1 dB for nitrocellulose membranes with targeted contrast. Enhancements of 36.0 +/- 2.3 dB and 8.5 +/- 0.9 dB for plasma and whole blood clots, respectively, were measured between 20 and 35 MHz. A proposed acoustic transmission line model predicted the targeted contrast system would increase the acoustic reflectivity of the nitrocellulose membrane, whole blood clot, and fibrin plasma clot by 2.6, 8.0, and 31.8 dB, respectively. These predictions were in reasonable agreement with the experimental results of this paper. In conclusion, acoustic microscopy provides a rapid and sensitive approach for in vitro chracterization, development, and testing of mathematical models of targeted contrast systems. Given the current demand for targeted contrast systems for medical diagnostic and therapeutic use, the use of acoustic microscopy may provide a useful tool in the development of these agents.

Acoustics↗
PubMed1998

Effects of tissue anisotropy on the spectral characteristics of ultrasonic backscatter measured with a clinical imaging system.

In this paper, we report the effects of inherent tissue anisotropy on the spectral properties of backscattered ultrasound when measured with a commercially-available imaging system. We insonified five specimens of bovine tendon immersed in a water tank and rotated in 10 degrees increments while being imaged with a Hewlett-Packard Sonos 1500 system. The backscattered RF signals corresponding to each angle of insonification were digitized and the spectral characteristics of the backscattered ultrasound were determined. The mean anisotropy, defined as the average difference between values at perpendicular and parallel insonification, for band-limited estimates of backscattered power, centroid frequency, upper-band to lower-band power ratio, and upper-band to total-band power ratio were found to be 24.6 +/- 1.1 dB, 142 +/- 27 kHz, 32 +/- 13%, and 22 +/- 5%, respectively (mean +/- SE). The magnitude of each of these backscatter spectral parameters was larger at perpendicular insonification compared with the corresponding values at parallel insonification, consistent with previous measurements of the inherent anisotropy of ultrasonic attenuation and backscatter in tissue.

Animals↗