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Selective ablation of matrix metalloproteinase-2 exacerbates experimental colitis: contrasting role of gelatinases in the pathogenesis of colitis.

The matrix metalloproteinases (MMPs), MMP-2 and MMP-9, share structural and substrate similarities and are up-regulated during human as well as animal models of inflammatory bowel disease. We recently demonstrated that epithelial-derived MMP-9 is an important mediator of inflammation and tissue damage in colitis. In this study, we examined the role of MMP-2 in acute colitis. Colitis was induced using two models, administration of dextran sodium sulfate (DSS) and Salmonella enterica subsp. serovar Typhimurium (S.T.). Bone marrow chimeras were performed using bone marrow cells from wild-type (WT) and MMP-2(-/-) mice. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, and histology. MMP-2 protein expression and activity were up-regulated in WT mice treated with DSS or S.T. MMP-2(-/-) mice were highly susceptible to the development of colitis induced by DSS (or S.T.) compared with WT. During inflammation, MMP-2 expression was increased in epithelial cells as well as in the infiltrating immune cells. Bone marrow chimera demonstrated that mucosa-derived MMP-2 was required for its protective effects toward colitis. Furthermore, we demonstrate that severe colitis in MMP-2(-/-) is not due to a compensatory increase in MMP-9. Finally, we show that MMP-2 regulates epithelial barrier function. In contrast to MMP-9, mucosa-derived MMP-2 may be a critical host factor that is involved in the prevention or cessation of the host response to luminal pathogens or toxins, an important aspect of healing and tissue resolution. Together, our data suggest that a critical balance between the two gelatinases determines the outcome of inflammatory response during acute colitis.

Acute Disease↗

Investigations of nicandrenone--a withanolide-like aromatic plant steroid from Nicandra physaloides.

On the basis of IR, UV, ORD, NMR and high resoluted mass spectral data as well as chemical transformations, evidence for structure 1 of the D-homo-aromatic plant steroid nicandrenone from Nicandra physaloides (Solanaceae) was given. The sterochemistry of both epoxy lactol functions in this compound was established using intramolecular hydrogen bonding investigations. Biogenetical aspects are discussed.

Chemical Phenomena↗

Child abduction: aged-based analyses of offender, victim, and offense characteristics in 550 cases of alleged child disappearance.

Crimes against children, particularly cases involving abduction and/or homicide, continue to be problematic as both a social phenomenon and judicial responsibility. Such cases routinely receive immense community and media attention and rapidly overwhelm investigative resources. Research in the area of childhood victimization, however, has only recently gained national prominence. While numerous studies on child abuse and neglect have been conducted, research on child abduction and homicide remains scant. Previous studies examining child abduction suffer from limited geographical scope or fail to base predictive analyses on victim characteristics. The current study reports the results of a nationally representative sample (47 states, the District of Columbia, and Puerto Rico) of 550 cases of alleged child abduction obtained from Federal Bureau of Investigation files for the period 1985 through 1995. Study results demonstrate that both offender and offense characteristics vary significantly according to victim age, gender, and race. Such differences appear critical to crime reconstruction, criminal profiling, and investigative resolution. Additionally, these data suggest that current child abduction prevention programs may emphasize inaccurate offender traits.

Adolescent↗

Nuclear medicine image registration by spatially noncoherent interferometry.

UNLABELLED: This article introduces a technique for obtaining high-resolution body contour data in the same coordinate frame as that of a rotating gamma camera, using a miniature range finder, the conoscope, mounted on the camera gantry. One potential application of the technique is accurate coregistration in longitudinal brain SPECT studies, using the face of the patient (or "mask"), instead of SPECT slices, to coregister subsequent acquisitions involving the brain. METHODS: Conoscopic holography is an interferometry technique that relies on spatially incoherent light interference in birefringent crystals. In this study, the conoscope was used to measure the absolute distance (Z) between a light source reflected from the skin and its observation plane. This light was emitted by a 0.2-mW laser diode. A scanning system was used to image the face during SPECT acquisition. The system consisted of a motor-driven mirror (Y axis) and the gamma-camera gantry (1 profile was obtained for each rotation step, X axis). The system was calibrated to place the conoscopic measurements and SPECT slices in the same coordinate frame. RESULTS: Through a simple and robust calibration of the system, the SE for measurements performed on geometric shapes was less than 2 mm, i.e., less than the actual pixel size of the SPECT data. Biometric measurements of an anthropomorphic brain phantom were within 3%-5% of actual values. The mask data were used to register images of a brain phantom and of a volunteer's brain, respectively. The rigid transformation that allowed the merging of masks by visual inspection was applied to the 2 sets of SPECT slices to perform the fusion of the data. CONCLUSION: At the cost of an additional low-cost setup integrated into the gamma-camera gantry, real-time data about the surface of the head were obtained. As in all other surface-based techniques (as opposed to volume-based techniques), this method allows the match of data independently from the dataset of interest and facilitates further registration of data from any other source. The main advantage of this technique compared with other optically based methods is the robustness of the calibration procedure and the compactness of the sensor as a result of the colinearity of the projected beam and the reflected (diffused) beams of the conoscope. Taking into account the experimental nature of this preliminary work, significant improvements in the accuracy and speed of measurements (up to 1000 points/s) are expected.

Brain↗

Are dermatologists in private practice interested in teledermatological services?

Diagnosing dermatologic skin conditions can be difficult, especially in pigmented skin lesions. Therefore, the consultation of an expert via teledermatology could prove vital. For this purpose, a rapid transfer of medical data including high resolution images is essential. This transfer can be performed with a variety of modern telecommunication technologies, including ISDN, highspeed-ISDN, Internet, and Intranet. As the levels of both communication software and camera-systems can be quite different, our survey investigated the equipment of 84 dermatologists in private practice. A questionnaire was distributed on computer equipment, operating system software, and any image documentation systems used, as well as required telecommunications equipment and possible applications of tele-dermatology. This survey showed a response rate of 54% and proves that dermatologists in private practice are interested in telemedicine services. Most dermatologists surveyed use Windows 95 operating software and 74% have access to modern ISDN modems or PC-cards. Dermatologists currently prefer applications with low-tech communication hardware and software requirements. Consultation of dermatological centers was the favored application with 59%. Our survey clearly demonstrates that a high percentage of dermatologists in private practice would use tele-dermatology. In our experience, for the excellence of this service an image documentation system is essential to provide the tele-dermatological expert with standardized images with constant illumination.

Dermatology↗

Coding and noncoding plastid DNA in palm systematics.

Plastid DNA sequences evolve slowly in palms but show that the family is monophyletic and highly divergent relative to other major monocot clades. It is therefore difficult to place the root within the palms because faster evolving, length-variable sequences cannot be aligned with outgroup monocots, and length-conserved regions have been thought to give too few characters to resolve basal nodes. To solve this problem, we combined 94 ingroup and 24 outgroup sequences from the length-conserved rbcL gene with ingroup and alignable outgroup sequences from noncoding rps16 intron and trnL-trnF regions. The separate rps16 intron and trnL-trnF region contained about the same number of variable sites (autapomorphies not included) as rbcL, but gave higher retention indices and more clades with bootstrap support. In general, the strict consensus tree based on combined rbcL, rps16 intron, and trnL-trnF data showed more resolution towards the base of the palm family than previous hypotheses of relationships of the Arecaceae. An important result was the position of subfamily Calamoideae as sister to the rest of the palms, but this received <50% bootstrap support. Another result of systematic significance was the indication that subfamily Phytelephantoideae is related to two tribes from subfamily Ceroxyloideae, Cyclospatheae and Ceroxyleae.

Journal Article↗

Multidetector-row spiral computed tomography in the diagnosis of thoracic diseases.

Since its introduction in 1992, spiral computed tomography (CT) scanners constructed with a single row of detectors have revolutionized imaging of thoracic diseases. Current state-of-the-art models use up to 16 detectors and are capable of acquiring 4 contiguous slices of data with each gantry rotation; systems with 8 data acquisition units (and more) are currently in development. The principal advantages offered by these systems are increased scanning speed and the ability to obtain volumetric data in high resolution. These features enable imaging with enhanced contrast concentration, decreased contrast load, decreased respiratory and cardiac motion artifact, and multiplanar and 3-dimensional reconstruction capabilities. Herein we first review the technical aspects of multidetector spiral CT scanning. The arrangement and various combinations of the detector rows are discussed. Key scanning variables, including collimation (slice thickness), pitch (the rate of table travel per gantry rotation divided by the beam collimation), and gantry speed, are briefly addressed in the context of their interrelationships. Comparison is made with single-detector-row systems to emphasize the superior scanning speed and resolution. We then discuss the various clinical applications of multidetector spiral CT, including CT pulmonary angiography, CT aortography, virtual bronchoscopy, and multiplanar and 3-dimensional reconstructions.

Angiography↗

Noise reduction in oncology FDG PET images by iterative reconstruction: a quantitative assessment.

UNLABELLED: Tumor detection depends on the contrast between tumor activity and background activity and on the image noise in these 2 regions. The lower the image noise, the easier the tumor detection. Tumor activity contrast is determined by physiology. Noise, however, is affected by many factors, including the choice of reconstruction algorithm. Previous simulation and phantom measurements indicated that the ordered-subset expectation maximization (OSEM) algorithm may produce less noisy images than does the usual filtered backprojection (FBP) method, at equivalent resolution. To see if this prediction would hold in actual clinical situations, we quantified noise in clinical images reconstructed with both OSEM and FBP. METHODS: Three patients (2 with colon cancer, 1 with breast cancer) were imaged with FDG PET using a "gated replicate" technique that permitted accurate measurement of noise at each pixel. Each static image was acquired as a gated image sequence, using a pulse generator with a 1-s period, yielding 40 replicate images over the 10- to 15-min imaging time. The images were or were not precorrected for attenuation and were reconstructed with both FBP and OSEM at comparable resolution. From these data, images of pixel mean, SD, and signal-to-noise ratio (S/N) could be produced, reflecting only noise caused by the statistical fluctuations in the emission process. RESULTS: Noise did not vary greatly over each FBP image, even when image intensity varied greatly from one region to the next, causing S/N to be worse in low-activity regions than in high-activity regions. In contrast, OSEM had high noise in hot regions and low noise in cold regions. OSEM had a much better S/N than did FBP in cold regions of the image, such as the lungs (in the attenuation-corrected images), where improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in hotter areas such as the liver (averaging 25% improvement in the attenuation-corrected images). In very hot tumors, FBP actually produced higher S/Ns than did OSEM. CONCLUSION: We conclude that OSEM reconstruction can significantly reduce image noise, especially in relatively low-count regions. OSEM reconstruction failed to improve S/N in very hot tumors, in which S/N may already be adequate for tumor detection.

Algorithms↗

[The RNA polymerase structure-activity studies (1962-2001)].

The study of RNA polymerase initiated by R.B. Khesin is conducted for about forty years at the laboratory founded by him (since 1989, in collaboration with A. Goldfarb's laboratory). Genetic methods are used in combination with methods of the specific chemical crosslinks of nucleic acids with proteins. The paper assesses the main results of the study in comparison with the X-ray crystallographic data of high resolution obtained recently. A short comparative summary of the RNA polymerase structure has been done for bacteria, archaebacteria, and eukaryotic organelles and nuclei. A brief history of the RNA polymerase study is also presented.

Crystallography, X-Ray↗

Image-based computational simulation of flow dynamics in a giant intracranial aneurysm.

BACKGROUND AND PURPOSE: Blood flow dynamics are thought to play an important role in the pathogenesis and treatment of intracranial aneurysms; however, hemodynamic quantities of interest are difficult to measure in vivo. This study shows that computational fluid dynamics (CFD) combined with computed rotational angiography can provide such hemodynamic information in a patient-specific and prospective manner. METHODS: A 58-year-old woman presented with partial right IIIrd cranial nerve palsy due to a giant carotid-posterior communicating artery aneurysm that was subsequently coiled. Computed rotational angiography provided high resolution volumetric image data from which the lumen geometry was extracted. This and a representative flow rate waveform were provided as boundary conditions for finite element CFD simulation of the 3D pulsatile velocity field. RESULTS: CFD analysis revealed high speed flow entering the aneurysm at the proximal and distal ends of the neck, promoting the formation of both persistent and transient vortices within the aneurysm sac. This produced dynamic patterns of elevated and oscillatory wall shear stresses distal to the neck and along the sidewalls of the aneurysm. These hemodynamic features were consistent with patterns of contrast agent wash-in during cine angiography and with the configuration of coil compaction observed at 6-month follow-up. CONCLUSION: Anatomic realism of lumen geometry and flow pulsatility is essential for elucidating the patient-specific nature of aneurysm hemodynamics. Such image-based CFD analysis may be used to provide key hemodynamic information for prospective studies of aneurysm growth and rupture or to predict the response of an individual aneurysm to therapeutic options.

Blood Flow Velocity↗

Histocompatibility testing.

The human leukocyte antigen (HLA) region on chromosome 6p21.3 is the most polymorphic in the human genome. It encodes hundreds of genes, of which the class I and class II HLA alleles play a central role in the generation of an immune response, but at the same time represent a barrier to marrow and organ transplantation. There is overwhelming evidence that optimal HLA matching will allow for safer marrow transplants, however with more than 1,200 allelic variants, the need to accurately identify the precise alleles is a technically demanding challenge. Methods currently in use for HLA typing include microcytotoxity assay, sequence-specific oligonucleotide (SSO) probe, sequence-specific primer (SSP) amplification, and sequence-based typing (SBT). Ambiguous results may still arise, even with the best molecular typing methods but this problem can be resolved by using a combination of methods. It is clear that a HLA typing laboratory will have to provide allele level resolution of HLA data using the most appropriate means available and this will have the greatest impact in terms of offering the best matched donor for the benefit of patients.

Alleles↗

[Utility of helical CT for the secondary mass screening of lung cancer].

From December 1991 to 1992, helical CT scan was performed in 55 patients with having abnormal shadow in the chest X-ray on the secondary screening for lung cancer. In all patients with suspected pulmonary lesions at first screening, helical CT scan was performed with 10 mm slice thickness for 300 mm. The moving speed of the patients table is 20 mm/l rot./1.5 sec for 300 mm in a single breath-hold. Helical CT allowed shortening of examination time and providing both better data continuity and resolution than conventional CT. In conclusion, helical CT can be useful for secondary screening of lung cancer but it was considered that there are some problems such as method of final pathological diagnosis and treatment for small nodular lesion.

Female↗

Software-enabled computed tomography analysis of the carotid artery and sphenoid sinus pneumatization patterns.

BACKGROUND: The critical relationship of the carotid artery with the sphenoid sinus has been long established. Sophisticated imaging software in conjunction with three-dimensional high-resolution computed tomography (CT) imaging now facilitates detailed analysis of these anatomic relationships. METHODS: Siemens VolumeZoom CT scanner was used to obtain high-resolution computed tomography data that was subsequently transferred to the CBYON Suite Doctor Station version 2.6 for analysis. Various surgical planning tools were used for evaluating the CT scans. The relationship of the carotid artery with the sphenoid sinus was delineated. RESULTS: One-hundred twenty-eight sides in 64 cadaveric specimens were reviewed. Pneumatization of the sphenoid sinus was classified into four categories: conchal, presellar, sellar, and postsellar. The incidence of these four types was 4.7, 4.7, 25, and 65%, respectively. Carotid artery exposure was categorized as follows: no exposure, <90 degrees, >90 to <180 degrees, and >180 degrees. The incidence of the carotid exposure was 12.5, 32.8, 50, and 4.7%, respectively. Septal insertions onto the carotid artery were noted in 37.5% and dehiscences in 19.5% of the specimens. CONCLUSION: Computer-aided CT analysis allows for a detailed study of the critical relationship of sphenoid pneumatization and carotid artery position. Such technology can be invaluable in surgical planning and navigation during endoscopic sinus surgery. In lieu of these findings, sinus surgeons must exercise extreme caution when operating in this region to prevent unintentional injury to the carotid artery.

Carotid Artery, Internal↗

From experimental imaging techniques to virtual embryology.

Modern embryology increasingly relies on descriptive and functional three dimensional (3D) and four dimensional (4D) analysis of physically, optically, or virtually sectioned specimens. To cope with the technical requirements, new methods for high detailed in vivo imaging, as well as the generation of high resolution digital volume data sets for the accurate visualisation of transgene activity and gene product presence, in the context of embryo morphology, were recently developed and are under construction. These methods profoundly change the scientific applicability, appearance and style of modern embryo representations. In this paper, we present an overview of the emerging techniques to create, visualise and administrate embryo representations (databases, digital data sets, 3-4D embryo reconstructions, models, etc.), and discuss the implications of these new methods on the work of modern embryologists, including, research, teaching, the selection of specific model organisms, and potential collaborators.

Computer Graphics↗

High-accuracy peak picking of proteomics data using wavelet techniques.

A new peak picking algorithm for the analysis of mass spectrometric (MS) data is presented. It is independent of the underlying machine or ionization method, and is able to resolve highly convoluted and asymmetric signals. The method uses the multiscale nature of spectrometric data by first detecting the mass peaks in the wavelet-transformed signal before a given asymmetric peak function is fitted to the raw data. In an optional third stage, the resulting fit can be further improved using techniques from nonlinear optimization. In contrast to currently established techniques (e.g. SNAP, Apex) our algorithm is able to separate overlapping peaks of multiply charged peptides in ESI-MS data of low resolution. Its improved accuracy with respect to peak positions makes it a valuable preprocessing method for MS-based identification and quantification experiments. The method has been validated on a number of different annotated test cases, where it compares favorably in both runtime and accuracy with currently established techniques. An implementation of the algorithm is freely available in our open source framework OpenMS.

Algorithms↗

Image guided stereotaxic surgery.

Computerized tomographic (CT) scanning and magnetic resonance imaging (MRI) can demonstrate areas of abnormal tissue within the brain, sometimes smaller than can be safely found and biopsied by open surgery or free-hand needle techniques. Image guided stereotaxic surgery can accurately and reproducibly place a needle in the brain based upon data from high resolution images. Tissue biopsy, abscess or cyst drainage, placement of radioactive seeds, or removal of a parenchymal hematoma can be done with less patient morbidity and in-hospital time.

Brain Neoplasms↗

[Amphibian bombesin and its analog alytesin].

A convenient route of synthesis of amphibian bombesin and bombesin-like peptide alytesin was found. These tetradecapeptides were obtained by assembling the 1-5 and 6-14 fragments by means of DCC-HONB or mixed anhydrides methods. Structure of the tetradecapeptides was confirmed by high resolution NMR spectroscopy data. The bombesin and alytesin synthesized potently decrease body temperature and stimulate pancreatic juice secretion.

Amino Acid Sequence↗

[Pulmonary scintigraphy using the inhalation of monodispersed radioactive aerosols. Preliminary report].

This article describes a method for inhalatory lung scintigraphy (ILS) by the use of radioactive monodisperse aerosols, with particles smaller than 2 microns. We discuss the findings in normal subjects, in patients with pulmonary embolism (PE) or/and obstructive pulmonary disease (OPD), and in individuals with severe pulmonary hypertension. This procedure has several advantages over the use of radioactive gases, such as 133Xe and 81Krm: lower cost, easier to perform, several scintigraphic projections in one study, acquisition of perfusion and inhalatory images in a single session, and inhalatory and perfusion images with identical spatial resolution and similar data density. It is concluded that ILS with radioactive monodisperse aerosols is a useful method for the study of OPD and in conjunction with perfusion lung scintigraphy is helpful in the diagnosis of PE.

Aerosols↗