Biomedical subjects

Mark Scott

Publications and source records attributed to Mark Scott.

7 recordsLinked to original sources

PubMed2005

3D modelling, gene expression mapping and post-mapping image analysis in the developing human brain.

As human brain development proceeds, there are complex changes in size and shape, most notably in the developing forebrain. Molecular technologies enable us to characterise the gene expression patterns that underlie these changes. To interpret these patterns the location of expression must be identified and, often, gene expression patterns compared for several genes or across several developmental stages. To facilitate interpretation we have generated a set of three-dimensional models using a recently developed technique, optical projection tomography. The models act as a framework onto which gene expression patterns are mapped and anatomical domains identified using custom-designed software, MAPaint. Here, we demonstrate their use to compare forebrain development at two embryonic stages (Carnegie stages 18 and 21; 44 and 52 days post conception, respectively) and as a means of recording, storing and visualising gene expression data for three example genes EMX1, EMX2 and OTX2. Anatomical domains were also mapped to the models and the comparison of gene expression and anatomical data is demonstrated at Carnegie stage 21. The three-dimensional models and sophisticated software facilitate the analysis and visualisation of morphological changes and gene expression patterns during early brain development and can be applied to the development of other complex structures.

Brain↗

PubMed2005

Dacron-covered stent-grafts in transjugular intrahepatic portosystemic shunts: initial experience.

PURPOSE: To retrospectively review the authors' experience with use of a Dacron-covered stent-graft in transjugular intrahepatic postosystemic shunts (TIPS). MATERIALS AND METHODS: The need for internal review board approval was waived. Informed consent was obtained from all patients. The study was compliant with the Health Insurance Portability and Accountability Act. A retrospective analysis was performed of 16 patients who received a Dacron-covered stent-graft during revision or de novo creation of TIPS. There were 13 men and three women aged 44-80 years (mean age, 61 years). Primary unassisted and assisted patency rates and secondary patency rates were estimated. The primary unassisted patency of patients who underwent de novo placement of stent-grafts (n = 10) was compared with that of patients with stent-grafts placed during shunt revision (n = 6); in all patients, stent-grafts were placed within stents. Primary unassisted patency was also compared between patients in whom the covered stent was confined to the parenchymal tract (n = 7) and those in whom the stent extended 1 cm or more into the portal vein (n = 9). Patency was estimated with the Kaplan-Meier method, and group comparisons were performed with the log-rank test. RESULTS: Primary unassisted patency rates following stent-graft placement at 4, 12, and 24 months (+/- standard error) were 64% +/- 14, 54% +/- 15, and 40% +/- 16, respectively. The rates for primary assisted patency were 78% +/- 12, 67% +/- 14, and 67% +/- 14 and those for secondary patency were 91% +/- 9, 81% +/- 12, and 54% +/- 23. At 12 months, primary unassisted patency with de novo stent-graft placement was 90% +/- 9, whereas that with stent-grafts placed during TIPS revision was 17% +/- 15 (P = .005). At 12 months, the primary unassisted patency in patients with stent-grafts confined to the parenchymal tract was 75% +/- 22, and that of patients with stent-grafts extending at least 1 cm into the portal vein was 40% +/- 17 (P = .21). CONCLUSION: In this small series, satisfactory long-term patency was observed among patients in whom Dacron-covered stent-grafts were placed during revision or de novo creation of TIPS. More favorable outcomes were observed when the stent-graft was placed during de novo TIPS creation and when the device was confined to the parenchymal tract.

Adult↗

PubMed2005

JAtlasView: a Java atlas-viewer for browsing biomedical 3D images and atlases.

BACKGROUND: Many three-dimensional (3D) images are routinely collected in biomedical research and a number of digital atlases with associated anatomical and other information have been published. A number of tools are available for viewing this data ranging from commercial visualization packages to freely available, typically system architecture dependent, solutions. Here we discuss an atlas viewer implemented to run on any workstation using the architecture neutral Java programming language. RESULTS: We report the development of a freely available Java based viewer for 3D image data, descibe the structure and functionality of the viewer and how automated tools can be developed to manage the Java Native Interface code. The viewer allows arbitrary re-sectioning of the data and interactive browsing through the volume. With appropriately formatted data, for example as provided for the Electronic Atlas of the Developing Human Brain, a 3D surface view and anatomical browsing is available. The interface is developed in Java with Java3D providing the 3D rendering. For efficiency the image data is manipulated using the Woolz image-processing library provided as a dynamically linked module for each machine architecture. CONCLUSION: We conclude that Java provides an appropriate environment for efficient development of these tools and techniques exist to allow computationally efficient image-processing libraries to be integrated relatively easily.

Anatomy↗

PubMed2004

Coronary flow velocity reserve does not correlate with TIMI frame count in patients undergoing non-emergency percutaneous coronary intervention.

OBJECTIVES: The purpose of this research was to compare the Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC) with coronary flow velocity reserve (CFVR) in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The relationship between CTFC and CFVR has not been adequately assessed in patients with coronary artery disease. METHODS: We studied 62 patients who underwent successful non-emergent PCI. All patients had Doppler evaluation of CFVR, CTFC, and quantitative coronary angiography. In an additional 17 patients, a frame count reserve was calculated as baseline CTFC/CTFC at peak hyperemia, induced by intracoronary adenosine after PCI. RESULTS: The CTFC decreased from 27 +/- 13 to 18 +/- 8, and CFVR increased from 1.5 +/- 0.4 to 2.6 +/- 0.7 (both p < 0.0001). The pre-PCI CTFC and the CFVR were closely related to minimal lumen diameter (p < 0.0001). After PCI, there was no correlation between CFVR and CTFC. In addition, no relationship was observed between CFVR and the frame count reserve. CONCLUSIONS: There was no significant correlation between CFVR and CTFC in patients undergoing coronary intervention. The relative utility of these measures in predicting outcomes in this setting requires further evaluation, but CTFC (or frame count reserve) does not appear to be an adequate surrogate measure of Doppler-derived CFVR.

Adenosine↗

PubMed2004

3 dimensional modelling of early human brain development using optical projection tomography.

BACKGROUND: As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped. RESULTS: Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (approximately 300 microm by approximately 150 microm) to the rootlets of cranial nerve XII (approximately 20 microm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is approximately 30 microm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated. CONCLUSION: In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of approximately 20 microm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development.

Brain↗

PubMed2004

Evaluating barriers to bioavailability in vivo: validation of a technique for separately assessing gastrointestinal absorption and hepatic extraction.

PURPOSE: The purpose of this study was to develop and validate a method for separately evaluating the roles of gastrointestinal absorption and hepatic extraction as barriers to oral bioavailability (BA). The method was validated using five reference compounds known to have different absorption and hepatic extraction properties. Dose-dependence was also investigated for one reference compound. METHODS: Five reference compounds, amoxicillin, antipyrine, atenolol, propranolol, and testosterone, were administered as a cassette intravenouly (IV), via the hepatoportal vein (IPV), intraduodenally (ID), and intracolonically (IC) to male Sprague-Dawley rats. Blood samples were taken at nine time points, and the compounds were extracted from plasma using solid phase extraction. Plasma concentrations of each compound were determined using Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Pharmacokinetic parameters including bioavailability were calculated for each compound for each route of administration. RESULTS: Testosterone BA was less than 10% by ID, IC, and IPV routes, due to high hepatic extraction, consistent with its high systemic clearance (63 ml x min(-1) x kg(-1)) and short terminal plasma half-life (23 min). The IPV BA of amoxicillin was 95%+/-6% indicating the absence of hepatic extraction in the rat, but with an ID BA of approximately 39% suggesting incomplete GI absorption to be the main barrier to bioavailability. Absorption was poor from the colon, demonstrating site-dependence consistent with literature reports of site-dependent absorption. Low oral BA of propranolol was due in part to first-pass hepatic extraction (IPV BA of 36%). The IPV BA of propranolol was dose-dependent, most likely due to saturation of the P450 enzymes. Atenolol was incompletely bioavailable due to incomplete intestinal absorption, with no contribution of hepatic first-pass metabolism. Antipyrine was highly bioavailable by all routes. CONCLUSIONS: This in vivo rat model is demonstrated to be useful for identifying and quantifying the causes of incomplete bioavailabilty. It separately evaluates intestinal absorption, hepatic extraction, and site-dependent absorption. Concentration-dependence of saturable processes can also be examined.

Amoxicillin↗

PubMed2003

Nuclear functions for plasma membrane-associated proteins?

There are a growing number of observations that proteins, which were initially thought to perform a specific function in a given subcellular compartment, may also play additional roles in different locations within the cell. Proteins found in adhesion and endocytic structures of the plasma membrane and which also traffic to the nucleus perhaps represent the more spectacular examples of this phenomenon. The mechanisms involved in the transport of these molecules through the nuclear pores and their potential nuclear functions are discussed.

Adherens Junctions↗