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PubMed1982

Two-dimensional echocardiography in experimental coronary stenosis. II. Relationship between systolic wall thinning and regional myocardial perfusion in severe coronary stenosis.

To determine if there is a quantitative relationship between systolic contraction abnormalities (demonstrated by two-dimensional echocardiography) and reduced myocardial perfusion in a setting of moderate and severe coronary stenosis, we created 70% or 90% reduction in circumflex coronary artery diameter in open-chest dogs. Transient ischemia was induced by superimposing increased myocardial oxygen requirements (i.v. isoproterenol, aortic constriction) in the presence of the stenosis or by decreased coronary perfusion (lowering arterial pressure with i.v. nitroprusside, nitroglycerin, or hemorrhage). Acute systolic wall thinning show by two-dimensional echocardiography or by implanted myocardial sonomicrometers was taken as functional evidence of myocardial ischemia. Myocardial perfusion was determined by radiolabeled microspheres when wall thinning was apparent. Systolic wall thinning could not be induced by these interventions when the degree of coronary stenosis was only 70%. Systolic wall thinning occurred only when increased myocardial oxygen requirements or decreased aortic pressure were superimposed on 90% coronary stenosis. Under these conditions, myocardial perfusion was reduced to 28 +/- 27 ml/100 g/min (mean +/- SD), 15--25% of control. Aortic diastolic pressure was a major determinant of ischemia in that contraction abnormalities produced by a 90% stenosis and vasodilators or hemorrhage could be acutely reversed by superimposing acute aortic constriction, which elevated arterial pressure; myocardial perfusion increased correspondingly. Thus, the demonstration of transient systolic wall thinning by two-dimensional echocardiography during a stressful intervention indicated that severe coronary stenosis was present, and that the perfusion of the acutely dyskinetic myocardial area was 25% of control or less.

Animals↗
PubMed2000

Regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing: a comparison with stress echocardiography and perfusion scintigraphy.

OBJECTIVES: We evaluated regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing. BACKGROUND: Evaluation and quantification of diastolic myocardial function remain a challenge for imaging techniques in stress tests. METHODS: A prospective study compared the detection of coronary artery stenosis: 1) by pulsed Doppler myocardial mapping, 2) by two-dimensional echocardiographic dobutamine stress test, and 3) by perfusion scintigraphy in 64 patients using coronary angiography for reference. An age matched subgroup of 10 patients with normal angiograms and two-dimensional echocardiographic stress test served as control group. Peak myocardial contraction velocity (Vc) and lengthening rate during early diastolic left ventricular (LV) filling (VE) were measured in 12 LV segments from three apical views. RESULTS: In controls, myocardial velocities increased during stress by > or =3.6 cm/s (p < 0.001). In LV segments depending on a stenosed artery (n = 70), VE decreased by > or =1 cm/s and, thus, was different from control segments (n = 112, p < 0.001) and from scar segments (n = 13, p < 0.01), whereas the change of Vc was similar to that in scar segments. A stress induced 2 cm/s reduction of VE discerned the best diagnostic accuracy (sensitivity 84%, specificity 93%) in comparison with two-dimensional echocardiography (78% and 71%) and perfusion scintigraphy (61% and 86%). Using receiver operating curves at incremental levels of luminal narrowing, these relations persisted. CONCLUSIONS: Quantification of diastolic myocardial function by pulsed Doppler myocardial mapping during dobutamine stress test was shown to be a feasible, accurate, reproducible, noninvasive technique that should be considered to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques for stress tests.

Cardiotonic Agents↗
PubMed1998

Dimensional stability of record bases fabricated from light-polymerized composite using two methods.

STATEMENT OF PROBLEM: Record bases fabricated from resin-based composite, which undergoes polymerization shrinkage during curing, can distort during curing to produce significant gaps along the posterior border. PURPOSE: This study evaluated the pattern of gap formation that occurs over the palatal area of a maxillary record base fabricated from light-cured composite (Triad), and determined whether changes in the fabrication method affects the size and pattern of gap formation. Effects of composite width and passage of time on gap formation were also analyzed. MATERIAL AND METHODS: Twenty record bases were fabricated with two methods: (1) according to the manufacturer's directions, the entire surface of the record base was exposed to the curing light; and (2) the palatal area of the record base was covered with foil to prevent light penetration, and the base was light cured in three stages with readaptation of the uncured composite between stages. Ten record bases from each group were tested 1 hour after fabrication; the remaining 10 from each group were tested 7 days after fabrication. Measurements of adaptation were made at three points representing the right and left ridge crests and midpalatal areas. The first measurement was taken at the posterior border and subsequent measurements were made at 5 mm increments after reduction of the posterior border of the cast and record base with a model trimmer. RESULTS: Dimensional changes were observed in both procedures. The largest discrepancy occurred at the posterior border of record bases fabricated using method 1. Mean gap formation at the posterior border in this group after 1 hour was 454, 729, and 334 microm and 483, 841, and 330 microm after 7 days at points A, B, and C, respectively. Record bases fabricated with procedure 2 demonstrated mean gap sizes at the posterior border after 1 hour of 219, 421, and 208 microm and 267, 403, and 192 microm after 7 days at points A, B, and C, respectively. No significant influence of composite width on gap size was found. CONCLUSION: The average gap size due to stage curing (method 2) was never greater than the corresponding gap that arose from the use of the manufacturer's recommendations (method 1). Limiting the amount of surface area exposed to the curing light and readapting the uncured composite to the cast between curing episodes can significantly reduce the mean gap size occurring at the posterior border.

Acrylic Resins↗
PubMed1993

Osteosynthesis of displaced intraarticular fractures of the calcaneus. Results in 123 cases.

The operative treatment of intraarticular calcaneal fractures has three principal aims: restoration of height, length, and width of the calcaneus, reconstruction of the subtalar and calcaneocuboid joint surfaces, and stable osteosynthesis using an H-plate or screws. In 68% of the cases, the sustentacular fragment was the key to open reduction, making the medial approach mandatory. In complex fractures, a lateral approach is added. In "blow-out" fractures or cases with comminution of the sustentacular fragment, an extended lateral approach only is used. For precise preoperative planning of roentgenograms in three planes, four Brodén's views and axial plus coroneal or three-dimensional computed tomography scans are required. From July 1983 to July 1990, 157 intraarticular calcaneal fractures were treated by open reduction. The results in 123 cases are 61% good or excellent, 32.5% satisfactory, and 6.5% poor. The following early complications occurred: superficial wound edge necrosis (8.3%), hematoma (2.5%), nonunion (1.3%), and infection (1.9%). Four patients (3.3%) in the follow-up group have developed degenerative changes severe enough to require subtalar fusion. To facilitate the comparison of results, new fracture classification and follow-up scoring systems have been devised.

Adolescent↗
PubMed2006

Peri-prosthetic bone density after implantation of a custom-made femoral component. A five-year follow-up.

Peri-prosthetic bone loss caused by stress shielding may be associated with aseptic loosening of femoral components. In order to increase primary stability and to reduce stress shielding, a three-dimensional, cementless individual femoral (Evolution K) component was manufactured using pre-operative CT scans. Using dual energy x-ray absorptiometry, peri-prosthetic bone density was measured in 43 patients, three months, six months, 3.6 and 4.6 years after surgery. At final follow-up there was a significant reduction in mean bone density in the proximal Gruen zones of -30.3% (zone 7) and -22.8% (zone 1). The density in the other zones declined by a mean of between -4% and -16%. We conclude that the manufacture of a three-dimensional, custom-made femoral component could not prevent a reduction in peri-prosthetic bone density.

Absorptiometry, Photon↗
PubMed2000

Structures of oxidized and reduced azurin II from Alcaligenes xylosoxidans at 1.75 A resolution.

Crystallographic structures of oxidized and reduced forms of azurin II are reported at 1.75 A resolution. Data were collected using one crystal in each case and by translating the crystal after each oscillation range to minimize photoreduction. Very small differences are observed at the Cu site upon reduction and these cannot be determined with confidence at current resolution. A comparison with the three-dimensional EXAFS reveals a good correspondence for all the ligand distances except for Cu-His46, where a larger deviation of approximately 0.12-0.18 A is observed, indicating that this ligand is more tightly restrained in the crystallographic refinement at the current resolution.

Alcaligenes↗
PubMed2006

Virtual 3-dimensional modeling as a valuable adjunct to aesthetic and reconstructive breast surgery.

Three-dimensional (3D) imaging technology currently is used by various commercial industries as a method for analyzing objects and shapes. Recent work from our group and others offer data to support the use of 3D imaging as a valuable tool in aesthetic and reconstructive breast surgery. We have developed a system for creating 3D breast models that provides clinical data that can help guide surgical management. With 3D breast models, surgeons are able to visually assess the size, shape, contour, and symmetry of the breast, as well as obtain quantitative breast measurements and volumetric calculations. Three-dimensional imaging may be applied to various plastic surgery procedures including breast reconstruction with implant/tissue expanders, local flap reconstruction, free-flap reconstruction, breast augmentation, and breast reduction surgery. The novel application of 3D imaging in these settings represents a significant advance from traditional approaches to aesthetic and reconstructive breast surgery in which surgical procedures are based on 2-dimensional photographs and visual size estimates.

Breast↗
PubMed1990

Functional significance of myocardial perfusion defects induced by dipyridamole using thallium-201 single-photon emission computed tomography and two-dimensional echocardiography.

The mechanisms responsible for inhomogeneous myocardial blood flow after oral administration of a large dose (300 mg) of dipyridamole were assessed in 27 patients with serial thallium-201 single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiograms. Myocardial tomographic images were obtained 50 minutes and 3 to 4 hours after administration of dipyridamole. Two-dimensional echocardiograms were recorded at baseline and then every 15 minutes for 60 minutes. Dipyridamole caused only a mild reduction in blood pressure (from 129 +/- 18 to 126 +/- 16 mm Hg) and a mild increase in heart rate (from 69 +/- 15 to 73 +/- 4 beats/min). Sixteen patients had perfusion defects after dipyridamole by SPECT, which underwent partial or total filling-in. Fourteen of these patients (87.5%) had either a new abnormality or further deterioration of a preexisting wall motion abnormality by 2-dimensional echocardiography, and thus were considered to have developed transient ischemia during dipyridamole administration. Ten of 11 patients (91%) with normal perfusion or fixed defects by SPECT had no further deterioration in wall motion after oral dipyridamole, and were thus considered to have no evidence of myocardial ischemia. In conclusion, most patients with transient thallium-201 defects after dipyridamole develop transient worsening of resting wall motion by 2-dimensional echocardiography, suggestive of true myocardial ischemia. Because myocardial oxygen demand, as indicated by the heart rate-blood pressure product, did not change significantly, the mechanism of myocardial ischemia in these patients is likely to be diminished regional blood flow related to a "subendocardial steal" induced by dipyridamole.

Angina Pectoris↗
PubMed1995

Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia.

Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used to measure membrane phospholipid metabolism and high-energy phosphate metabolism in the left and right frontal lobes of 27 schizophrenic patients. In the schizophrenic patients, the phosphomonoester peak area was decreased in bilateral frontal lobes compared with that in age-matched normal subjects. On the other hand, the peak area of beta-adenosine triphosphate was increased in the left frontal lobe in the schizophrenic group. The phosphocreatine peak area was increased in the left frontal lobe of schizophrenic patients with high scores on the Scale for the Assessment of Negative Symptoms (SANS).

Adenosine Triphosphate↗
PubMed2003

Influence of surfactant-facilitated interfacial tension reduction on chlorinated solvent migration in porous media: observations and numerical simulation.

The ability of a multiphase flow model to capture the migration behavior of chlorinated solvents under conditions of surfactant-facilitated interfacial tension (IFT) reduction is assessed through comparison of model predictions with observations from controlled laboratory experiments. Tetrachloroethene (PCE) was released in two-dimensional saturated systems, packed with sandy media that incorporated rectangular lenses of capillary contrast. Spatially uniform interfacial tension conditions were created in the tanks by pre-flushing the porous medium with either Milli Q water or an aqueous surfactant solution. Experimental observations showed that surfactant-facilitated IFT reductions substantially lowered capillary resistance to the vertical downward migration of PCE and enabled PCE to enter finer grained, less permeable lenses that were not penetrated in the absence of surfactant. An immiscible flow model was used to simulate the conditions of the laboratory experiments. Under higher IFT conditions (47.5 and 5 dyn/cm), the model could successfully predict the general migration behavior of the organic liquid. Model predictions, however, exhibited poorer agreement with observed migration pathways under low IFT conditions (0.5 dyn/cm). In all cases, the predicted PCE distributions were influenced by selection of the parametric model for capillary retention and relative permeability. Simulated migration rates were more consistent with observed behavior when the Brooks-Corey/Burdine model was employed. For low interfacial tensions, improved predictions of migration pathways were obtained through grid refinement and incorporation of small-scale packing variability. Simulations highlight the substantial sensitivity of model predictions to the capillary pressure-scaling factor, grid resolution, and small-scale porosity variations at interfaces of permeability contrast under reduced IFT conditions.

Chlorine Compounds↗
PubMed2000

Tissue responses to molecularly reinforced polylactide-co-glycolide implants.

Plates for internal fixation fabricated from biodegradable polymers degrade via an autocatalytic route. When they are used in bone implants of significant size and thickness, hollowing of the implant may occur while the overall dimensions appear unchanged. We hypothesized that incorporation of a cross-linked polypropylene fumarate matrix into polylactide-co-glycolide bone plates may provide an internal molecular network which prevents implant collapse. Cross-linking reagents of varying hydrophilicity including N-vinylpyrrolidone (VP), hydroxyethylmethacrylate (HEMA), and ethyleneglycol dimethacrylate (EGDMA) were employed. With the objective of determining the most biocompatible and structurally sound composition for molecular reinforcement, we investigated tissue responses in both subcutaneous and orthotopic rodent implantation models in relation to maintenance of implant integrity by histologic, histomorphometric, and stereomicroscopic analysis. Results showed that tissue responses were correlated with dimensional stability of the implants. The most favorable results were seen with the hydrophobic cross-linker EGDMA; this may have been related to the initial reduction of the water uptake by the implant. Cross-linking of polypropylene fumarate with EGDMA within a polylactide-co-glycolide bone plate may offer a means to maintain excellent biocompatibility while improving dimensional stability of biodegradable bone plates.

Animals↗
PubMed1992

Alterations in tumor angiogenesis associated with stable expression of the HIV tat gene.

Recent evidence suggests that the human immunodeficiency virus type 1 (HIV) trans-activator gene (tat) has transforming properties and may be a causative factor in the development of certain types of cancers, in particular Kaposi's sarcoma (i.e., Vogel J. et al. Nature 335:606-611, 1988). To help elucidate the potential role or roles of the HIV tat gene in neoplastic transformation, cell lines were constructed that constitutively express a functional tat gene product. HeLa cells were coelectroporated with two plasmids, one containing the HIV tat gene in an expression cassette and another containing the dominant selectable marker gene xanthine guanine phosphoribosyltransferase (XGPRT). After XGPRT selection, single-cell clones that expressed a functional tat protein were identified by measuring chloramphenicol acetyltransferase (CAT) activity after electroporating a plasmid containing the CAT gene transcriptionally controlled by HIV trans-activation-responsive region (tar). Phenotypic alterations resulting from the expression of tat were then determined. Control cells and tat-expressing cells grew at similar rates in culture. However, when grown as tumors in nude mice, tat-expressing cells produced a lower percentage of tumors, and the tumors that were produced either regressed, stopped growing, or grew at a very reduced rate compared with cells not expressing tat. These differences may have resulted from a tat-associated reduction in neovascularization in the tumors. A comparison of total cellular proteins by two-dimensional polyacrylamide gel electrophoresis indicated only one reproducible alteration in a polypeptide of approximately 44 kDa and pl of approximately 6.2 associated with tat expression. These cells may be very useful in future in vitro and in vivo studies designed to examine the effects of HIV tat on endothelial and vascular smooth-muscle cells and the role of tat in the etiology of Kaposi's sarcoma.

Animals↗
PubMed1997

Combination of antitumor ether lipid with lipids of complementary molecular shape reduces its hemolytic activity.

Because the therapeutic use of the antitumor ether lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine (ET-18-OCH3) is restricted by its hemolytic activity we explored the use of lipid packing parameters to reduce this toxicity by creating structurally optimized ET-18-OCH3 liposomes. We postulated that combination of ET-18-OCH3, which is similar in structure to lysophosphatidylcholine, with lipid molecules of complementary molecular shape (opposite headgroup/chain volume) would likely yield a stable lamellar phase from which ET-18-OCH3 exchange to red blood cell membranes would be curtailed. To quantitate the degree of shape complementarity, we used a Langmuir trough and measured the mean molecular area per molecule (MMAM) for monolayers comprised of ET-18-OCH3, the host lipids, and binary mixtures of varying mole percentage ET-18-OCH3. The degree of complementarity was taken as the reduction in MMAM from the value expected based on simple additivity of the individual components. The greatest degree of shape complementarity was observed with cholesterol: the order of complementarity for the ET-18-OCH3-lipid mixtures examined was cholesterol >> DOPE > POPC approximately DOPC. Phosphorus NMR and TLC analysis of aqueous suspensions of ET-18-OCH3 (40 mol%) with the host lipids revealed them to all be lamellar phase. For ET-18-OCH3 at 40 mol% in liposomes, the hemolytic activity followed the trend of the reduction in MMAM and was least for the ET-18-OCH3/cholesterol system (H50 = 661 microM ET-18-OCH3) followed by ET-18-OCH3/DOPE (H50 = 91 microM) and mixtures with POPC and DOPC which were comparable at H50 = 26 microM and 38 microM, respectively: the H50 concentration for free ET-18-OCH3 was 16 microM. This experimental strategy for designing optimized liposomes with a reduction in exchange, and hence toxicity, may be useful for other amphipathic/lipophilic drugs that are dimensionally compatible with lipid bilayers.

Antineoplastic Agents↗
PubMed2001

Numerical analysis of biological clogging in two-dimensional sand box experiments.

Two-dimensional models for biological clogging and sorptive trace transport were used to study the progress of clogging in a sand box experiment. The sand box had been inoculated with a strip of bacteria and exposed to a continuous injection of nitrate and acetate. Brilliant Blue was regularly injected during the clogging experiment and digital images of the tracer movement had been converted to concentration maps using an image analysis. The calibration of the models to the Brilliant Blue observations shows that Brilliant Blue has a solid biomass dependent sorption that is not compliant with the assumed linear constant Kd behaviour. It is demonstrated that the dimensionality of sand box experiments in comparison to column experiments results in a much lower reduction in hydraulic conductivity (factor of 100) and that the bulk hydraulic conductivity of the sand box decreased only slightly. However, in the central parts of the clogged area, the observations and simulations clearly show a complex picture of flow diverting the injected nutrients around the clogged area as fingers. The calibration of the model demonstrates that the physical and microbiological processes (advection, dispersion, attachment-detachment, growth-decay) are all needed to capture the progress of clogging.

Acetates↗
PubMed1998

Proton translocation by bacteriorhodopsin and heme-copper oxidases.

Proton translocation is the means by which free energy is conserved from oxygen reduction by the respiratory heme-copper oxidases and from sunlight by bacteriorhodopsin. Three-dimensional structures at atomic resolution of both proteins have aided functional studies of the proton translocation mechanism. A comparison reveals common structural and functional features that may be unique to the primary proton pumps in biology.

Bacteriorhodopsins↗
PubMed2001

Characterization of the Mycobacterium tuberculosis H37Rv alkyl hydroperoxidase AhpC points to the importance of ionic interactions in oligomerization and activity.

An alkyl hydroperoxidase (AhpC) has been found frequently to be overexpressed in isoniazid-resistant strains of Mycobacterium tuberculosis. These strains have an inactivated katG gene encoding a catalase peroxidase, which might render mycobacteria susceptible to the toxic peroxide radicals, thus leading to the concomitant overexpression of the AhpC. Although the overexpressed AhpC in isoniazid-resistant strains of M. tuberculosis may not directly participate in isoniazid action, AhpC might still assist M. tuberculosis in combating oxidative damage in the absence of the catalase. Here we have attempted to characterize the AhpC protein biochemically and report its functional and oligomerization properties. The alkyl hydroperoxidase of M. tuberculosis is unique in many ways compared with its well-characterized homologues from enteric bacteria. We show that AhpC is a decameric protein, composed of five identical dimers held together by ionic interactions. Dimerization of individual subunits takes place through an intersubunit disulphide linkage. The ionic interactions play a significant role in enzymic activity of the AhpC protein. The UV absorption spectrum and three-dimensional model of AhpC suggest that interesting conformational changes may take place during oxidation and reduction of the intersubunit disulphide linkage. In the absence of the partner AhpF subunit in M. tuberculosis, the mycobacterial AhpC might use small-molecule reagents, such as mycothiol, for completing its enzymic cycle.

Biopolymers↗
PubMed2002

The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae.

The Brucella BvrR/BvrS two-component regulatory system is homologous to the ChvI/ChvG systems of Sinorhizobium meliloti and Agrobacterium tumefaciens necessary for endosymbiosis and pathogenicity in plants. BvrR/BvrS controls cell invasion and intracellular survival. Probing the surface of bvrR and bvrS transposon mutants with monoclonal antibodies showed all described major outer membrane proteins (Omps) but Omp25, a protein known to be involved in Brucella virulence. Absence of Omp25 expression was confirmed by two-dimensional electrophoresis of envelope fractions and by gene reporter studies. The electrophoretic analysis also revealed reduction or absence in the mutants of a second set of protein spots that by matrix-assisted laser desorption ionization MS and peptide mass mapping were identified as a non-previously described Omp (Omp3b). Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface-targeted bactericidal peptides, it is proposed that BvrR/BvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments. A genomic search revealed that Omp25 (Omp3a) and Omp3b belong to a family of Omps of plant and animal cell-associated alpha-Proteobacteria, which includes Rhizobium leguminosarum RopB and A. tumefaciens AopB. Previous work has shown that RopB is not expressed in bacteroids, that AopB is involved in tumorigenesis, and that dysfunction of A. tumefaciens ChvI/ChvG alters surface properties. It is thus proposed that the BvrR/BvrS and Omp3 homologues of the cell-associated alpha-Proteobacteria play a role in bacterial surface control and host cell interactions.

Bacterial Outer Membrane Proteins↗
PubMed2002

Ionizing radiation activates nuclear protein phosphatase-1 by ATM-dependent dephosphorylation.

Ionizing radiation (IR) is known to activate multiple signaling pathways, resulting in diverse stress responses including apoptosis, cell cycle arrest, and gene induction. IR-activated cell cycle checkpoints are regulated by Ser/Thr phosphorylation, so we tested to see if protein phosphatases were targets of an IR-activated damage-sensing pathway. Jurkat cells were subjected to IR or sham radiation followed by brief (32)P metabolic labeling. Nuclear extracts were subjected to microcystin affinity chromatography to recover phosphatases, and the proteins were analyzed by two-dimensional gel electrophoresis. Protein sequencing revealed that the microcystin-bound proteins with the greatest reduction in (32)P intensity following IR were the alpha and delta isoforms of protein phosphatase 1 (PP1). Both of these PP1 isoforms contain an Arg-Pro-Ile/Val-Thr-Pro-Pro-Arg sequence near the C terminus, a known site of phosphorylation by Cdc/Cdk kinases, and phosphorylation attenuates phosphatase activity. In wild-type Jurkat cells or ataxia telangiectasia (AT) cells that are stably transfected with full-length ATM kinase, IR resulted in net dephosphorylation of this site in PP1 and produced activation of PP1. However, in AT cells that are deficient in ATM, IR failed to induce dephosphorylation or activation of PP1. IR-induced PP1 activation in the nucleus may be a critical component in an ATM-mediated pathway controlling checkpoint activation.

Amino Acid Sequence↗