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PubMed1992

[An autopsy case of spinal subdural abscess in the aged--comparative study with neuroradiological findings].

An 82-year-old woman without previous medical problem noticed vague back pain on December 31, 1989, and was admitted to a hospital because she developed a fever, a rapidly progressive weakness followed by anesthesia of the lower extremities and sphincter disturbance. On myelography and myelo-CT, the spinal cord appeared to be displaced by an extramedullary mass which partially blocked the subdural space at the level of T-9 to L-1. When transferred to our hospital on January 8, 1990, she was febrile and complaining of headache with meningeal signs. Percussion tenderness was present at T-8 to L-1 spinal spinous process. Neurological examination revealed that the patient had mild consciousness clouding, total paraplegia in the legs, sensory disturbance of a partial degree at L-1 to L-3 and totally below L-3, brisk but equal tendon reflexes in the upper extremities, areflexia in the legs with positive bilateral Babinski signs and sphincter disturbance. Otherwise she was neurologically unremarkable. Acute inflammatory reactions were prominent among the laboratory findings on admission. A lumbar tap yielded purulent fluid with more than 170,000 cells/mm3, 5,000 mg/dl of protein, 44 mg/dl of glucose and culture of the fluid isolated Escherichia coli. T1-weighted sagittal MRI disclosed an ill defined mass which showed the same or locally higher with gadopentetate dimeglumine (Gd-DTPA) signal intensity as soft tissue, compressing the spinal cord anteriorly from T-7 to L-3. The lesion was noticed to have a more extensive rostral-caudal extent than was inferred from myelography and myelo-CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2000

Creation of radiofrequency lesions in a porcine model: correlation with sonography, CT, and histopathology.

OBJECTIVE: We studied the correlation between sonographic and CT appearances of radiofrequency thermal lesions created in porcine liver and histopathologic findings to evaluate the accuracy of these techniques in revealing the extent of tissue necrosis. MATERIALS AND METHODS: We used sonographic guidance and a 2.0-cm-diameter, eight-prong retractable radiofrequency electrode to view 12 hepatic lesions that were created in five pigs. Biphasic helical CT was performed 12-48 hr after ablation. The animals were sacrificed immediately after CT, and their livers were histopathologically examined. The maximum lesion size in the long and short axes as measured on CT and sonography was then correlated with the histopathologically determined lesion size. RESULTS: On sonography, lesions changed rapidly within 5 min after the termination of ablation. An early echogenic cloud became peripherally hypoechoic with a variable thin echogenic rim. Early (0-2 min after ablation) sonograms led to an underestimation of true lesion sizes on histopathology (r = 0.3-0.49; p < 0.05). Delayed (2-5 min after ablation) sonograms also led to an underestimation of true lesion size (r = 0.5-0.62; p < 0.05); however, lesions were larger and better demarcated. Biphasic contrast-enhanced helical CT revealed avascular lesions surrounded by hyperemic rims that closely correlated with true pathologic lesions size (r = 0.93-0.95; p < 0. 05). Lesions with hyperemic rims that were measured on CT led to overestimations of true lesion size. CONCLUSION: Sonography led to underestimations of the true size of ablated lesions within the first 5 min after creation; however, delayed images provided better results. The avascular lesion measured on contrast-enhanced helical CT closely correlated with the size of ablated tissue; therefore, contrast-enhanced CT is preferred for serially monitoring the effect of radiofrequency ablation.

Animals↗
PubMed2005

Compensating for intraoperative soft-tissue deformations using incomplete surface data and finite elements.

Image-guided liver surgery requires the ability to identify and compensate for soft tissue deformation in the organ. The predeformed state is represented as a complete three-dimensional surface of the organ, while the intraoperative data is a range scan point cloud acquired from the exposed liver surface. The first step is to rigidly align the coordinate systems of the intraoperative and preoperative data. Most traditional rigid registration methods minimize an error metric over the entire data set. In this paper, a new deformation-identifying rigid registration (DIRR) is reported that identifies and aligns minimally deformed regions of the data using a modified closest point distance cost function. Once a rigid alignment has been established, deformation is accounted for using a linearly elastic finite element model (FEM) and implemented using an incremental framework to resolve geometric nonlinearities. Boundary conditions for the incremental formulation are generated from intraoperatively acquired range scan surfaces of the exposed liver surface. A series of phantom experiments is presented to assess the fidelity of the DIRR and the combined DIRR/FEM approaches separately. The DIRR approach identified deforming regions in 90% of cases under conditions of realistic surgical exposure. With respect to the DIRR/FEM algorithm, subsurface target errors were correctly located to within 4 mm in phantom experiments.

Algorithms↗
PubMed1998

Comparison of models used for UV index calculations.

Eighteen radiative transfer models in use for calculation of UV index are compared with respect to their results for more that 100 cloud-free atmospheres, which describe present, possible future and extreme conditions. The comparison includes six multiple-scattering spectral models, eight fast spectral models and four empirical models. Averages of the results of the six participating multiple-scattering spectral models are taken as a basis for assessment. The agreement among the multiple-scattering models is within +/- 0.5 UV index values for more than 80% of chosen atmospheric parameters. The fast spectral models have very different agreement, between +/- 1 and up to 12 UV index values. The results of the empirical models agree reasonably well with the reference models but only for the atmospheres for which they have been developed. The data to describe the atmospheric conditions, which are used for the comparison, together with the individual results of all participating models and model descriptions are available on the Internet: http://www.meteo.physik.uni-muenchen.de/++ +strahlung/cost/.

Computer Simulation↗
PubMed1999

Deriving meteorological variables across Africa for the study and control of vector-borne disease: a comparison of remote sensing and spatial interpolation of climate.

This paper presents the results of an investigation into the utility of remote sensing (RS) using meteorological satellites sensors and spatial interpolation (SI) of data from meteorological stations, for the prediction of spatial variation in monthly climate across continental Africa in 1990. Information from the Advanced Very High Resolution Radiometer (AVHRR) of the National Oceanic and Atmospheric Administration's (NOAA) polar-orbiting meteorological satellites was used to estimate land surface temperature (LST) and atmospheric moisture. Cold cloud duration (CCD) data derived from the High Resolution Radiometer (HRR) on-board the European Meteorological Satellite programme's (EUMETSAT) Meteosat satellite series were also used as a RS proxy measurement of rainfall. Temperature, atmospheric moisture and rainfall surfaces were independently derived from SI of measurements from the World Meteorological Organization (WMO) member stations of Africa. These meteorological station data were then used to test the accuracy of each methodology, so that the appropriateness of the two techniques for epidemiological research could be compared. SI was a more accurate predictor of temperature, whereas RS provided a better surrogate for rainfall; both were equally accurate at predicting atmospheric moisture. The implications of these results for mapping short and long-term climate change and hence their potential for the study and control of disease vectors are considered. Taking into account logistic and analytical problems, there were no clear conclusions regarding the optimality of either technique, but there was considerable potential for synergy.

Africa↗
PubMed2005

Dynamical variability in the modelling of chemistry-climate interactions.

We have used a version of the Met Office's climate model, into which we have introduced schemes for atmospheric chemistry, to study chemistry-dynamics-climate interactions. We have considered the variability of the stratospheric polar vortex, whose behaviour influences stratospheric ozone loss and will affect ozone recovery. In particular, we analyse the dynamical control of high latitude ozone in a model version which includes an assimilation of the equatorial quasi-biennial oscillation (QBO), demonstrating the stability of the linear relation between vortex strength and high latitude ozone. We discuss the effect of interactive model ozone on polar stratospheric cloud (PSC) area/volume and winter-spring stratospheric ozone loss in the northern hemisphere. In general we find larger polar ozone losses calculated in those model integrations in which modelled ozone is used interactively in the radiation scheme, even though we underestimate the slope of the ozone loss per PSC volume relation derived from observations. We have also looked at the influence of changing stratosphere-to-troposphere exchange on the tropospheric oxidizing capacity and, in particular, have considered the variability of tropospheric composition under different climate regimes (El Niño/La Niña, etc.). Focusing on the UT/LS, we show the response of ozone to El Niño in two different model set-ups (tropospheric/ stratospheric). In the stratospheric model set-up we find a distinct signal in the lower tropical stratosphere, which shows an anti-correlation between the Niño 3 index and the ozone column amount. In contrast ozone generally increases in the upper troposphere of the tropospheric model set-up after an El Niño. Understanding future trends in stratospheric ozone and tropospheric oxidizing capacity requires an understanding of natural variability, which we explore here.

Air Pollutants↗
PubMed1985

[A case favorably progressed after operation for hypertensive intracerebral hemorrhage showed extravasation on angiogram occurred in chronic alcoholism].

It is said that the prognosis is generally unfavorable in patients with hypertensive intracerebral hemorrhage showed extravasation on angiogram. Recently, we experienced a case whose prognosis was eventful after the removal of hematoma. So we reported this case and discussed between alcoholism and intracerebral hemorrhage accompanied with extravasation on angiogram in this paper. A 59-year-old male was transferred to our emergency center because of right hemiplegia and mild clouding of consciousness at around nine in the evening on December 12, 1983. At the time of admission, his neurological state was classified into grade II, exhibiting the right putamenal hemorrhage and pyramidal destruction type of hematoma by CT scan with 58 ml of hematoma volume. The right carotid angiography was immediately performed and confirmed the hematoma being of lateral type. At that time, extravasation proximal to the lateral lenticulostriate artery was noted. Repeated CT scan revealed the enlarged hematoma (105 ml) accompanying with ventricular hemorrhage. At the completion of these examinations, the neurological grade was III. The hematoma was surgically removed after 4 hours following the onset of cerebral hemorrhage. His postoperative course was very favorable. Although acute hydrocephalus appeared later on, it was cured by ventricular drainage. The patient become possible to walk with a helper by 1 month after operation. CT scan obtained 1 month after operation revealed a remarkable brain atrophy, which was probably derived from chronic alcoholism.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed2005

A method to track cortical surface deformations using a laser range scanner.

This paper reports a novel method to track brain shift using a laser-range scanner (LRS) and nonrigid registration techniques. The LRS used in this paper is capable of generating textured point-clouds describing the surface geometry/intensity pattern of the brain as presented during cranial surgery. Using serial LRS acquisitions of the brain's surface and two-dimensional (2-D) nonrigid image registration, we developed a method to track surface motion during neurosurgical procedures. A series of experiments devised to evaluate the performance of the developed shift-tracking protocol are reported. In a controlled, quantitative phantom experiment, the results demonstrate that the surface shift-tracking protocol is capable of resolving shift to an accuracy of approximately 1.6 mm given initial shifts on the order of 15 mm. Furthermore, in a preliminary in vivo case using the tracked LRS and an independent optical measurement system, the automatic protocol was able to reconstruct 50% of the brain shift with an accuracy of 3.7 mm while the manual measurement was able to reconstruct 77% with an accuracy of 2.1 mm. The results suggest that a LRS is an effective tool for tracking brain surface shift during neurosurgery.

Algorithms↗
PubMed2002

Three-dimensional ultrastructural analysis of RNA distribution within germinal granules of Xenopus.

The germ plasm is a specialized region of oocyte cytoplasm that contains determinants of germ cell fate. In Xenopus oocytes, the germ plasm is a part of the METRO region of mitochondrial cloud. It contains the germinal granules and a variety of coding and noncoding RNAs that include Xcat2, Xlsirts, Xdazl, DEADSouth, Xpat, Xwnt11, fatVg, B7/Fingers, C10/XFACS, and mitochondrial large and small rRNA. We analyzed the distribution of these 11 different RNAs within the various compartments of germ plasm during Xenopus oogenesis and development by using whole-mount electron microscopy in situ hybridization. Serial EM sections were used to reconstruct a three-dimensional image of germinal granule distribution within the METRO region of the cloud and the distribution of RNAs on the granules in oocytes and embryos. We found that, in the oocytes, the majority of RNAs were associated either with the precursor of germinal granules or with the germ plasm matrix. Only Xcat2, Xpat, and DEADSouth RNAs were associated with the mature germinal granules in oocytes, while only Xcat2 and Xpat were associated with germinal granules in embryos. However, Xcat2 was the only RNA that was consistently sequestered inside the germinal granules, while the others were located on the periphery. Xdazl, which functions in germ cell migration/formation, was detected on the matrix between granules. Later in development, Xcat2 mRNA was released from the germinal granules. This coincides with the timing of its translational derepression. These results demonstrate that there is a dynamic three-dimensional architecture to the germinal granules that changes during oogenesis and development. They also indicate that association of specific RNAs with the germinal granules is not a prerequisite for their serving a germ cell function; however, it may be related to their state of translational repression.

Animals↗
PubMed1998

Viewer-centered temporal biasing of 3-D rotation percepts.

The perceived direction of rotation of a 3-D cloud of dots can be biased by a prior rotation (Jiang, Pantle, and Mark, 1998 Perception & Psychophysics 60 275-286). In a series of experiments, it is shown that the temporal rotation bias is reversed by a 180 degrees change of head orientation between two rotation sequences; i.e. the perceived direction of rotation reverses for the second of two sequences when head orientation is changed. The bias is, therefore, viewer-centered. Perceptual reversals are not obtained when the orientation of the head is changed and returned to its original position between rotation sequences. It was also found that the viewer-centered bias combined additively with viewer-independent near-far luminance information. Finally, the bias was manifest when 3-D depth was re-established, but not maintained, between rotation sequences. A model, in descriptive and flowchart forms, is used to explain the integration of world-centered information and a viewer-centered temporal bias on the presence/absence of perceptual reversals of the rotating virtual sphere. In the model, the temporal bias is the result of the coupling of depth values to persisting 2-D retinal motion signals.

Computer Graphics↗
PubMed2005

High diversity of oilseed rape pollen clouds over an agro-ecosystem indicates long-distance dispersal.

Abstract Estimating the frequency of long-distance pollination is important in cultivated species, particularly to assess the risk of gene transfer following the release of genetically modified crops. For this purpose, we estimated the diversity and origin of fertilizing pollen in a 10 x 10 km French oilseed rape production area. First, the cultivar grown in each field was identified through surveys to farmers and using microsatellite markers. Examination of the seed set in fields indicated high rates of seed contamination (8.7%) and pollination from other sources (5%). Then, male-sterile plants were scattered over the study area and their seed genotyped using the same markers. Most pollination was local: 65% of the seeds had a compatible sire in the closest field, i.e. at 50 or 300 m depending on site, but the nearest compatible field was found more than 1000 m away for 13% of the seeds. To assess the diversity of fertilizing pollen, each seed was assigned to the nearest putative siring cultivar. The observed diversity of pollen was then compared to that predicted by simulations using three empirical dispersal models with increasing proportion of long-distance pollination. The diversity was sensitive to the dispersal kernel used in the simulations, fatter-tailed functions predicting higher diversities. The dispersal kernel that was more consistent with our data predicted more long-distance dispersal than the exponential function.

Agriculture↗
PubMed1992

Nizatidine versus placebo in active benign gastric ulcer disease: an eight-week, multicenter, randomized, double-blind comparison. The Nizatidine Benign Gastric Ulcer Disease Study Group.

STUDY OBJECTIVE: To determine if 150 mg nizatidine twice daily or 300 mg nizatidine at bedtime are similarly effective and to compare each dose with placebo in healing benign gastric ulcers and relieving peptic ulcer symptoms. METHODS: This study was a randomized, double-blind, placebo-controlled parallel comparison. The study was conducted at 74 gastroenterology and internal medicine clinics in the United States and Canada. Four hundred fifty-six patients with active benign gastric ulcer documented by endoscopy participated in the study. On the basis of a computer-generated randomization list, patients were assigned sequentially to receive either 150 mg nizatidine twice daily (n = 151), 300 mg nizatidine once daily at bedtime and identically appearing placebo capsules in the morning (n = 153), or placebo capsules twice daily (n = 152). Treatment lasted for 8 weeks unless healing was documented by endoscopy after 4 weeks. Antacid tablets (aluminum hydroxide, magnesium hydroxide, simethicone combination) were supplied for relief of symptoms. MEASUREMENTS AND MAIN RESULTS: Both doses of nizatidine significantly improved healing rates at 8 weeks compared with placebo. Daytime and nighttime symptom severity was improved by both nizatidine regimens at end point (p less than 0.015 versus placebo, two-tailed test). Antacid use was similar for all groups in the end point analysis. Patient well-being was significantly better in patients treated with nizatidine than in patients in the placebo group ((p less than 0.04, two-tailed test). No clinically significant differences in the incidence of adverse clinical or laboratory events were noted. CONCLUSION: Nizatidine, 300 mg at bedtime and 150 mg twice daily, resulted in greater healing of benign gastric ulcers than placebo treatment after 8 weeks. Relief of the symptoms of gastric ulcer was significantly better in the patients receiving nizatidine treatment versus placebo treatment.

Capsules↗
PubMed2004

Visualization of regulated exocytosis with a granule-membrane probe using total internal reflection microscopy.

Secretory granules labeled with Vamp-green fluorescent protein (GFP) showed distinct signatures upon exocytosis when viewed by total internal reflection fluorescence microscopy. In approximately 90% of fusion events, we observed a large increase in fluorescence intensity coupled with a transition from a small punctate appearance to a larger, spreading cloud with free diffusion of the Vamp-GFP into the plasma membrane. Quantitation suggests that these events reflect the progression of an initially fused and spherical granule flattening into the plane of the plasma membrane as the Vamp-GFP simultaneously diffuses through the fusion junction. Approximately 10% of the events showed a transition from puncta to ring-like structures coupled with little or no spreading. The ring-like images correspond quantitatively to granules fusing and retaining concavity (recess of approximately 200 nm). A majority of fusion events involved granules that were present in the evanescent field for at least 12 s. However, approximately 20% of the events involved granules that were present in the evanescent field for no more than 0.3 s, indicating that the interaction of the granule with the plasma membrane that leads to exocytosis can occur within that time. In addition, approximately 10% of the exocytotic sites were much more likely to occur within a granule diameter of a previous event than can be accounted for by chance, suggestive of sequential (piggy-back) exocytosis that has been observed in other cells. Overall granule behavior before and during fusion is strikingly similar to exocytosis previously described in the constitutive secretory pathway.

Animals↗
PubMed1989

[Acute encephalopathy with symmetrical, widespread, edematous and necrotic lesions--an autopsy case report].

A 67-year-old, non-alcoholic Japanese female case with liver cirrhosis, in the course of admission due to ascites and rupture of the rectal varix, was affected by an unusual type of acute progressive encephalopathy, presenting inattentiveness and slurred speech as initial symptoms. Her consciousness was increasingly clouded. Variable symptoms such as saccadic eye movement, nystagmus, weakness, hyperreflexia, dysmetria, adiadochokinesis and painful dysesthesia were also noted. Laboratory examination disclosed abnormal liver functions, hyponatremia, respiratory alkalosis and normal blood ammonia. Cerebrospinal fluid was xanthochromic and contained slightly increased protein. On CT scan, bilateral symmetrical low density areas were demonstrated in the diencephalon, brainstem and cerebellum. A week after the onset, she was comatose with rigidity of the extremities. Hyperbilirubinemia and severe hyponatremia developed. On the second CT, low density areas extended to the cerebral deep white matter. Her respiration became irregular, and she expired 16 days after the onset. Autopsy disclosed edematous lesions with dark brown discoloration in the medial basal ganglia, ventral diencephalon and mesencephalic tegmentum. Less severely affected lesions with pale yellow discoloration extended into the cerebral white matter, pontine and medullar tegmentum and cerebellar dentate nuclei. In the central lesions, diapedesis of erythrocytes and serum-plasma was marked, with necrosis of the neurons. In the peripheral lesions, diapedesis of less proteinaceous fluid was noted, with less severe neuronal damages. Neither capillary prominence nor gliosis was remarkable. The clinical and pathological features of the present case bore some similarity to those of Wernicke's and Leigh's encephalopathies. However, the patient's age, habitus or clinical course was atypical for the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2005

Interfacial tryptophan residues: a role for the cation-pi effect?

Integral membrane proteins are characterized by having a preference for aromatic residues, e.g., tryptophan (W), at the interface between the lipid bilayer core and the aqueous phase. The reason for this is not clear, but it seems that the preference is related to a complex interplay between steric and electrostatic forces. The flat rigid paddle-like structure of tryptophan, associated with a quadrupolar moment (aromaticity) arising from the pi-electron cloud of the indole, interacts primarily with moieties in the lipid headgroup region hardly penetrating into the bilayer core. We have studied the interaction between the nitrogen moiety of lipid molecule headgroups and the pi-electron distribution of gramicidin (gA) tryptophan residues (W9, W11, W13, and W15) using molecular dynamics (MD) simulations of gA embedded in two hydrated lipid bilayers composed of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) and 1-palmitoyl-2-oleoylphosphatidyl-choline (POPC), respectively. We use a force field model for tryptophan in which polarizability is only implicit, but we believe that classical molecular dynamics force fields are sufficient to capture the most prominent features of the cation-pi interaction. Our criteria for cation-pi interactions are based on distance and angular requirements, and the results from our model suggest that cation-pi interactions are relevant for W(PE)1), W(PE)13, W(PE)15, and, to some extent, W(PC)11 and W(PC)13. In our model, W9 does not seem to engage in cation-pi interactions with lipids, neither in POPE nor POPC. The criteria for the cation-pi effect are satisfied more often in POPE than in POPC, whereas the H-bonding ability between the indole donor and the carbonyl acceptor is similar in POPE and POPC. This suggests an increased affinity for lipids with ethanolamine headgroups to transmembrane proteins enriched in interfacial tryptophans.

Amino Acids↗
PubMed2001

Congenital hereditary endothelial dystrophy and band keratopathy in an infant with corpus callosum agenesis.

PURPOSE: To report the features of a syndrome of endothelial failure and band-shaped keratopathy in an infant with corpus callosum agenesis. METHODS: The clinical and histopathologic features of an infant presenting with bilateral corneal clouding and corpus callosum agenesis are reported. The patient underwent bilateral penetrating keratoplasty at ages 28 months and 4 years. Light and electron microscopy were used to characterize the structural changes. RESULTS: The epithelium was thin and degenerate. Bowman's membrane contained spherical aggregates that were present also within a connective tissue pannus. The midstroma was normal, but there were floral and rope-like aggregations of collagen in the pre-Descemet's membrane region. Under electron microscopy, the spherules formed target-shaped lesions with a central focus of alternating electron-dense and lucent material. Numerous microfilaments in the pannus and anterior stroma labeled with fibrillin-1 antibody. Microfilaments within fibroblasts were stained with vimentin antibody. Posteriorly, the endothelium was mainly absent and Descemet's membrane showed a fetal layer and a posterior collagenous layer. CONCLUSION: Corneal appearances in this patient were in keeping with those of congenital hereditary endothelial corneal dystrophy. However, there was no family history and neither parent showed a clinical endothelial abnormality. The presence of fetal, banded material in Descemet's membrane suggested that endothelial loss began at or near the time of birth. The band keratopathy was regarded as a secondary change. The association with corpus callosum agenesis does not appear to have been described previously.

Agenesis of Corpus Callosum↗
PubMed2004

Drug delivery to the nasal cavity: in vitro and in vivo assessment.

Drugs are given intranasally for both local and systemic applications, and the use of the intranasal route is predicted to rise dramatically in the next 10 years. Nasal drug delivery may be assessed by a variety of means, but high reliance is often placed upon in vitro testing methodology (emitted dose, droplet or particle size distribution, spray pattern, and plume geometry). Spray pattern and plume geometry define the shape of the expanding aerosol cloud, while droplet size determines the likelihood of deposition within the nasal cavity by inertial impaction. Current FDA guidance recommends these methods as a means of documenting bioavailability (BA) and bioequivalence (BE) for topically acting solution formulations, because they can be performed reproducibly and are more discriminating among products. Nasal drug delivery in vivo may be determined by several radionuclide imaging methods: the two-dimensional imaging technique of gamma scintigraphy has been used most widely, but the three-dimensional method of positron emission tomography (PET) is being used increasingly often. In some situations a good in vitro/in vivo correlation (IVIVC) exists; for instance, negligible penetration into the lungs has been demonstrated in the case of nasal pump sprays delivering large droplets, while a clear difference may be shown in intranasal deposition between two aerosols with markedly different size distributions. However, recent studies have shown a poorer IVIVC for two similar nasal pump sprays, where significant differences in in vitro parameters were not reflected in differences in nasal deposition in vivo. It is suggested that radionuclide imaging data may have an important role to play as an adjunct to in vitro testing in BA and BE assessments and may provide a clearer understanding of the changes in in vitro parameters that are important for predicting differences in in vivo performance.

Administration, Intranasal↗
PubMed2002

Search for potential vaccine candidate open reading frames in the Bacillus anthracis virulence plasmid pXO1: in silico and in vitro screening.

A genomic analysis of the Bacillus anthracis virulence plasmid pXO1, aimed at identifying potential vaccine candidates and virulence-related genes, was carried out. The 143 previously defined open reading frames (ORFs) (R. T. Okinaka, K. Cloud, O. Hampton, A. R. Hoffmaster, K. K. Hill, P. Keim, T. M. Koehler, G. Lamke, S. Kumano, J. Mahillon, D. Manter, Y. Martinez, D. Ricke, R. Svensson, and P. J. Jackson, J. Bacteriol. 181:6509-6515, 1999) were subjected to extensive sequence similarity searches (with the nonredundant and unfinished microbial genome databases), as well as motif, cellular location, and domain analyses. A comparative genomics analysis was conducted with the related genomes of Bacillus subtilis, Bacillus halodurans, and Bacillus cereus and the pBtoxis plasmid of Bacillus thuringiensis var. israeliensis. As a result, the percentage of ORFs with clues about their functions increased from approximately 30% (as previously reported) to more than 60%. The bioinformatics analysis permitted identification of novel genes with putative relevance for pathogenesis and virulence. Based on our analyses, 11 putative proteins were chosen as targets for functional genomics studies. A rapid and efficient functional screening method was developed, in which PCR-amplified full-length linear DNA products of the selected ORFs were transcribed and directly translated in vitro and their immunogenicities were assessed on the basis of their reactivities with hyperimmune anti-B. anthracis antisera. Of the 11 ORFs selected for analysis, 9 were successfully expressed as full-length polypeptides, and 3 of these were found to be antigenic and to have immunogenic potential. The latter ORFs are currently being evaluated to determine their vaccine potential.

Animals↗