Search PubMed⌕ Search

Biomedical subjects

D G Heath

Publications and source records attributed to D G Heath.

At least 19 recordsLinked to original sources
PubMed1999

Immune response to Yersinia outer proteins and other Yersinia pestis antigens after experimental plague infection in mice.

There is limited information concerning the nature and extent of the immune response to the virulence determinants of Yersinia pestis during the course of plague infection. In this study, we evaluated the humoral immune response of mice that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Such a model may replicate the clinical situation in humans and indicate which virulence determinants are expressed in vivo. Immunoglobulin G enzyme-linked immunosorbent assay and immunoblotting were performed by using purified, recombinant antigens including F1, V antigen, YpkA, YopH, YopM, YopB, YopD, YopN, YopE, YopK, plasminogen activator protease (Pla), and pH 6 antigen as well as purified lipopolysaccharide. The major antigens recognized by murine convalescent sera were F1, V antigen, YopH, YopM, YopD, and Pla. Early treatment with antibiotics tended to reduce the immune response and differences between antibiotic treatment regimens were noted. These results may indicate that only some virulence factors are expressed and/or immunogenic during infection. This information may prove useful for selecting potential vaccine candidates and for developing improved serologic diagnostic assays.

Animals↗
PubMed1999

Renal artery stenosis: CT angiography--comparison of real-time volume-rendering and maximum intensity projection algorithms.

PURPOSE: To compare results of helical computed tomographic (CT) angiography with real-time interactive volume rendering (VR) to CT angiography with maximum intensity projection (MIP) for the detection of renal artery stenosis. MATERIALS AND METHODS: Twenty-five patients underwent both conventional and CT angiography of the renal arteries. Images were blindly reviewed after rendering with MIP and VR algorithms. MIP images were viewed in conjunction with axial CT images; VR models were evaluated in real time at the workstation without CT images. Findings in 50 main and 11 accessory renal arteries were categorized as normal or by degree of stenosis. RESULTS: All arteries depicted on conventional angiograms were visualized on MIP and VR images. Receiver operating characteristic (ROC) analysis for MIP and VIR images demonstrated excellent discrimination for the diagnosis of stenosis of at least 50% (area under the ROC curve, 0.96-0.99). Although sensitivity was not significantly different for VR and MIP (89% vs 94%, P > .1), specificity was greater with VR (99% vs 87%, P = .008 to .08). Stenosis of at least 50% was overestimated with CT angiography in four accessory renal arteries, but three accessory renal arteries not depicted at conventional angiography were depicted at CT angiography. CONCLUSION: In the evaluation of renal artery stenosis, CT angiography with VR is faster and more accurate than CT angiography with MIP. Accessory arteries not depicted with conventional angiography were depicted with both CT angiographic algorithms.

Adult↗
PubMed1999

CT angiography with volume rendering for quantifying vascular stenoses: in vitro validation of accuracy.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of CT angiography with volume rendering for quantifying vascular stenoses in vitro. MATERIALS AND METHODS: Vascular models with three degrees of stenosis (33%, 67%, and 83%) were imaged at three orientations to the axial plane (parallel, perpendicular, or 45 degrees ) using helical CT with 2-mm collimation and two pitches (1 or 2), two reconstruction intervals (1 or 2 mm), and two scan times (.75 or 1 sec). Diameter and percentage of stenosis were measured from volume renderings using full width at half maximum. Images were measured in two planes whenever resolution varied with direction. Statistical analysis was performed using analysis of variance. RESULTS: Mean absolute error of the measured percentage of stenosis was 7% (range, 0-27%). The actual percentage of stenosis and vessel orientation had the most significant effects on accuracy (p < .001). The measured percentage of stenosis was significantly less accurate with phantoms parallel to the axial plane than with other orientations (p < .001). Mean absolute error in the measured percentage of stenosis was 4% when the parallel-to-the-axial-plane orientation was excluded. Overlapping (1-mm) reconstructions were significantly more accurate than 2-mm reconstructions (p < .05) and direction of measurement significantly affected accuracy (p < .05), but these effects were secondary. CONCLUSION: CT angiography with volume rendering can accurately quantify vascular stenoses, but it is less accurate for vessels in the axial plane. With 2-mm collimation, vessel characteristics have greater effects on accuracy than do acquisition parameters.

Analysis of Variance↗
PubMed1998

Evaluating the potential and problems of three-dimensional computed tomography measurements of arterial stenosis.

Volume visualization is gaining widespread acceptance in medical applications. As its use increases, the issue of accuracy becomes critical. There have been very few studies examining the accuracy of volume rendering techniques. We studied the accuracy of hardware-assisted volume rendering for measurement of arterial stenosis in computed tomography (CT) data. The results of our study reveal that accurate measurements can be made from volume rendered CT data. However, error is present (absolute average error from 5.1% to 13.6%) and there is some variability, even for experts (standard deviation ranged from 4.8% to 15%). The evidence suggests that the choice of volume rendering (transfer function) parameters greatly affects the accuracy of the results. Accurate transfer function parameter selection is a difficult problem. Parameters that produce realistic images often provide inaccurate measurements. As the use of volume visualization grows and more inexperienced users begin using these tools for medical diagnosis and staging, new guidelines, aids, and techniques must be developed to ensure reliable, accurate visualization results.

Angiography↗
PubMed1998

Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine.

The current human whole-cell vaccine is ineffective against pneumonic plague caused by typical F1 capsule positive (F1+) strains of Yersinia pestis. The authors found this vaccine to also be ineffective against F1-negative (F1-) Y. pestis strains, which have been isolated from a human case and from rodents. For these reasons, the authors developed a recombinant vaccine composed of a fusion protein of F1 with a second protective immunogen, V antigen. This vaccine protected experimental mice against pneumonic as well as bubonic plague produced by either an F1+ or F1- strain of Y. pestis, gave better protection than F1 or V alone against the F1+ strain, and may provide the basis for an improved human plague vaccine.

Aerosols↗
PubMed1998

Abdominal image segmentation using three-dimensional deformable models.

RATIONALE AND OBJECTIVES: The authors develop a three-dimensional (3-D) deformable surface model-based segmentation scheme for abdominal computed tomography (CT) image segmentation. METHODS: A parameterized 3-D surface model was developed to represent the human abdominal organs. An energy function defined on the direction of the image gradient and the surface normal of the deformable model was introduced to measure the match between the model and image data. A conjugate gradient algorithm was adapted to the minimization of the energy function. RESULTS: Test results for synthetic images showed that the incorporation of surface directional information improved the results over those using only the magnitude of the image gradient. The algorithm was tested on 21 CT datasets. Of the 21 cases tested, 11 were evaluated visually by a radiologist and the results were judged to be without noticeable error. The other 10 were evaluated over a distance function. The average distance was less than 1 voxel. CONCLUSIONS: The deformable model-based segmentation scheme produces robust and acceptable outputs on abdominal CT images.

Algorithms↗
PubMed1998

Portal venous system thrombosis: helical CT angiography before transjugular intrahepatic portosystemic shunt creation.

PURPOSE: To evaluate the utility of helical computed tomographic (CT) angiography for depiction of thrombi in the portal venous system in patients under consideration for transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: Contrast material-enhanced helical CT was performed before TIPS creation in 25 patients. Axial, multiplanar, and three-dimensional images were evaluated to determine whether thrombus was present in the portal system and whether TIPS creation was contraindicated. CT findings were confirmed at visceral angiography (n = 3), direct portography (n = 20), or duplex ultrasonography (n = 2). RESULTS: Ten (40%) of 25 patients, including 10 (56%) of 18 patients with refractory variceal hemorrhage, had thrombus in the portal venous system. Helical CT scans depicted thrombus in nine (90%) of 10 patients (95% confidence interval = 0.71, 1.00) and in 16 (94%) of 17 vessels (95% confidence interval = 0.83, 1.00), including the portal vein (eight of eight patients), splenic vein (three of four patients), and superior mesenteric vein (five of five patients). TIPS creation was canceled in four (16%) patients on the basis of CT findings. CONCLUSION: Thrombi in the portal venous system are common in patients with refractory variceal hemorrhage. Helical CT angiography is sensitive and specific for portal venous system thrombosis and can provide information that alters treatment in these patients.

Contraindications↗
PubMed1998

Short- and long-term efficacy of single-dose subunit vaccines against Yersinia pestis in mice.

A single, subcutaneous, 30-microg dose of either a combination of the Yersinia pestis proteins F1+V or a F1-V fusion protein adsorbed to the adjuvant aluminum hydroxide, protected Hsd:ND4 mice for one year against pneumonic plague. The recombinant F1+V vaccine provided significant protection as early as day 14 postimmunization. The current Plague Vaccine USP in a single 0.2-ml dose did not provide significant protection in this mouse model. Antibody titers to F1 and V peaked at approximately 5-12 weeks postimmunization and were still detectable one year later. These F1 and V subunit vaccines may offer effective long-term immunity with a reduced dosage schedule when compared with the presently licensed, formalin-killed, whole-cell vaccine.

Animals↗
PubMed1997

Three-dimensional CT stereoscopic visualization of renal masses: impact on diagnosis and patient treatment.

OBJECTIVE: The objective of this study was to determine whether three-dimensional reconstruction with stereoscopic display of helical CT data sets and CT angiography are useful in the examination of patients with known or suspected renal masses. CONCLUSION: Volume-rendering techniques applied to helical CT data sets coupled with three-dimensional stereoscopic imaging provide a complete examination of patients with known or suspected renal masses. Such information can help guide patient treatment and provide a single preoperative study when nephron-sparing surgery or total nephrectomy is considered.

Adult↗
PubMed1996

Skeletal 3-D CT: advantages of volume rendering over surface rendering.

Both surface rendering and volume rendering have been extensively applied to CT data for 3-D visualization of skeletal pathology. The review illustrates potential limitations of each technique by directly comparing 3-D images of bone pathology created using volume rendering and surface rendering. Surface rendering show gross 3-D relationships most effectively, but suffer from more stairstep artifacts and fail to effectively display lesions hidden behind overlying bone or located beneath the bone cortex. Volume-rendering algorithms effectively show subcortical lesions, minimally displaced fractures, and hidden areas of interest with few artifacts. Volume algorithms show 3-D relationships with varying degrees of success depending on the degree of surface shading and opacity. While surface rendering creates more three-dimensionally realistic images of the bone surface, it may be of limited clinical utility due to numerous artifacts and the inability to show subcortical pathology. Volume rendering is a flexible 3-D technique that effectively displays a variety of skeletal pathology with few artifacts.

Algorithms↗
PubMed1996

Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge.

As a first step in formulating an improved plague vaccine, we developed a simple purification strategy that produced high yields of pure cell-associated and culture supernatant-derived fraction 1 capsular antigen (F1) from both avirulent Yersinia pestis C092 (Pgm- Lcr-) and an Escherichia coli F1-producing recombinant strain. Cell-associated F1 was partially purified by sequential ammonium sulfate precipitations of a sodium chloride extract of acetone-dried bacteria harvested from broth cultures. Cell-free F1 was precipitated directly from culture supernatants with a single application of 30% ammonium sulfate. By exploiting the aggregative property of F1, large quantities of purified high-molecular-weight F1 species from both cell extracts and supernatants were isolated in the void volume of a preparative gel filtration column. Highly purified, endotoxin-free F1, combined with two different adjuvants, induced very high F1 titers in mice and protected them against either subcutaneous (70 to 100% survival) or aerosol (65 to 84% survival) challenge with virulent organisms. This protection was independent of the source of the antigen and the adjuvant used. F1-induced protection against both subcutaneous and aerosol challenge was also significantly better than that conferred by immunization with the licensed killed whole-cell vaccine. Our results indicate that F1 antigen represents a major protective component of previously studied crude capsule preparations, and immunity to F1 antigen provides a primary means for the host to overcome plague infection by either the subcutaneous or respiratory route.

Animals↗
PubMed1996

CT angiography with volume rendering: advantages and applications in splanchnic vascular imaging.

The authors compared volume rendering with maximum intensity projection (MIP) and shaded surface display as a technique for generating three-dimensional (3D) images of the vasculature from spiral computed tomography (CT) data sets. In four patients with pathologic splanchnic vasculature, the advantages of volume-rendered display are illustrated for depiction of 3D vascular anatomy, vascular and visceral interrelationships, variant vasculature, tumor encasement, and hepatic tumor localization for presurgical planning.

Abdomen↗
PubMed1996

Automatic liver segmentation technique for three-dimensional visualization of CT data.

PURPOSE: To develop a system for automatic segmentation of the liver from computed tomographic (CT) scans of the abdomen for three-dimensional volume-rendering displays. MATERIALS AND METHODS: An automated liver segmentation system was developed, which combined domain knowledge with analysis of a global histogram, morphologic operators, and the parametrically deformable contour model. Boundaries of the thresholded liver volume were modified section-by-section by exploiting information from adjacent sections. These boundaries were refined by optimization of the parametrically deformable contour model. Volume-rendered images were created by using the boundaries to exclude tissues outside the liver. The system was tested on CT data sets from 10 cases of potentially resectable hepatic neoplasm. RESULTS: Of the 401 sections in the 10 cases, 53 sections (13.2%) required user modifications during segmentation. The utility of the three-dimensional-rendered images with use of these liver boundaries was judged by a radiologist as being comparable to that of three-dimensional images created with manual editing. Twenty-eight of the sections were deemed imperfect by the radiologist and might need further modifications. CONCLUSION: An effective technique for automatic segmentation of the liver from CT images has been developed. This technique promises to save time and simplify the creation of three-dimensional liver images by minimizing operator intervention.

Humans↗
PubMed1995

Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis.

Yersinia pestis, the causative agent of plague, possesses multiple virulence determinants encoded on its three plasmids and on its chromosome. We evaluated the role of the protein capsule F1 in virulence an immunity against plague. Strains lacking F1, either those that are naturally occurring or those with genetically defined nonpolar mutations in the structural gene, retained their virulence for mice and nonhuman primates. However, both active immunization with F1, from either a recombinant vector or Y. pestis, and passive immunization with F1 monoclonal antibody protected mice from experimental infection with wild-type F1-positive organisms. These results suggest that protective immunogens like F1 need not be essential for virulence. The rare isolation of virulent F1-negative organisms from F1-immunized animals infected with F1-positive strains supports this conclusion and also suggests that, in addition to F1, an optimal vaccine against plague should include essential virulence factors as immunogens.

Animals↗
PubMed1995

Phase variation of Enterococcus faecalis pAD1 conjugation functions relates to changes in iteron sequence region.

pAD1 (60 kb) is a conjugative, hemolysin/bacteriocin plasmid in Enterococcus faecalis. It confers a mating response to the peptide sex pheromone cAD1 produced by recipient (plasmid-free) cells, leading to highly efficient plasmid transfer in broth matings. Control of the physiological response to cAD1 can been overridden by a reversible phase variation event at frequencies on the order of 10(-4) to 10(-3) per cell per generation (L. T. Pontius and D. B. Clewell, Plasmid 26:172-185, 1991). The variant forms are designated Dryc and Dry+, which reflects the colony morphologies of cells whose conjugation functions are switched on and off, respectively. Here we show that Dryc variants exhibit a structural change in a region between repA and repB that contains two clusters of 8-bp iterons. The change involved a 31- or 32-bp increase in size of this region. In three or four independent variants examined, one of the iteron clusters increased in size from 13 to 17 iterons. When iteron DNA was placed on a multicopy plasmid and introduced into a wild-type pAD1 derivative, the Dryc phenotype was generated. Since traA, a key negative regulator of conjugation, bears several centrally located iteron-like sequences with the same orientation, we speculate that the protein(s) that normally binds iterons (possibly RepA and/or RepB) blocks traA transcription in Dryc variants.

Bacterial Proteins↗
PubMed1995

Three-dimensional spiral CT during arterial portography: comparison of three rendering techniques.

The three most common techniques for three-dimensional reconstruction are surface rendering, maximum-intensity projection (MIP), and volume rendering. Surface-rendering algorithms model objects as collections of geometric primitives that are displayed with surface shading. The MIP algorithm renders an image by selecting the voxel with the maximum intensity signal along a line extended from the viewer's eye through the data volume. Volume-rendering algorithms sum the weighted contributions of all voxels along the line. Each technique has advantages and shortcomings that must be considered during selection of one for a specific clinical problem and during interpretation of the resulting images. With surface rendering, sharp-edged, clear three-dimensional reconstruction can be completed on modest computer systems; however, overlapping structures cannot be visualized and artifacts are a problem. MIP is computationally a fast technique, but it does not allow depiction of overlapping structures, and its images are three-dimensionally ambiguous unless depth cues are provided. Both surface rendering and MIP use less than 10% of the image data. In contrast, volume rendering uses nearly all of the data, allows demonstration of overlapping structures, and engenders few artifacts, but it requires substantially more computer power than the other techniques.

Algorithms↗