Publications by authors named "Kenneth J Longmuir"

Tumor models in mice offer opportunities for understanding tumor formation and development of therapeutic treatments for hepatocellular carcinoma. In this study, subcutaneous or intra-hepatic Hepa129 tumors were established in C3H mice. Tumor growth was determined by daily measurements of subcutaneous tumors and post-mortem studies of subcutaneous and intrahepatic tumors.

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Intravascular injections of fluorescent or biotinylated tomato lectin were tested to study labeling of vascular elements in laboratory mice. Injections of Lycopersicon esculentum agglutinin (tomato lectin) (50-100 µg/100 µl) were made intravascularly, through the tail vein, through a cannula implanted in the jugular vein, or directly into the left ventricle of the heart. Tissues cut for thin 10- to 12-µm cryostat sections, or thick 50- to 100-µm vibratome sections, were examined using fluorescence microscopy.

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In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ∼20 screens of information, on the subjects of the CO2-bicarbonate buffer system, other body buffer systems, and acid-base disorders. Five clinical case modules were also developed.

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Background: Kupffer cells are well known macrophages of the liver, however, the developmental characteristics of Kupffer cells in mice are not well understood. To clarify this matter, the characteristics of Kupffer macrophages in normal developing mouse liver were studied using light microscopy and immunocytochemistry.

Methods: Sections of liver tissue from early postnatal mice were prepared using immunocytochemical techniques.

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Background: Liposomes incorporating peptide from the Plasmodium circumsporozoite protein (CSP) accumulate rapidly and selectively in adult mouse liver.

Purpose: The development of the liposome-binding pattern in liver and spleen was studied in relationship to the development of extracellular matrix molecules.

Methods: Liposomes were administered to mice intravascularly or applied to the surface of liver and spleen slices in vitro.

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Previous work demonstrated that liposomes, containing an amino acid sequence that binds to hepatic heparan sulfate glycosaminoglycan, show effective targeting to liver hepatocytes. These liposomes were tested to determine whether they can deliver doxorubicin selectively to liver and hepatocytes in vivo. Fluid-phase liposomes contained a lipid-anchored 19-amino acid glycosaminoglycan targeting peptide.

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The cellular organization of normal mouse liver was studied using light and electron microscopy and quantitative immunocytochemical techniques. The general histological organization of the mouse liver is similar to livers of other mammalian species, with a lobular organization based on the distributions of portal areas and central venules. The parenchymal hepatocytes were detected with immunocytochemical techniques to recognize albumin or biotin containing cells.

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An analytical model of mixing in the staggered herringbone mixer (SHM) was derived to estimate mixing parameters and provide practical expressions to guide mixer design and operation for a wide range of possible solutes and flow conditions. Mixing in microfluidic systems has historically been characterized by the mixing of a specific solute system or by the redistribution of flow streams; this approach does not give any insight into the ideal operational parameters of the mixer with an arbitrary real system. For Stokes-flow mixers, mixing can be computed from a relationship between solute diffusivity, flow rate, and mixer length.

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This report describes the development and evaluation of a range of polyethyleneglycol and polyethyleneglycol-peptide liposome formulations that effectively target liver in vivo. A 19-amino-acid sequence from the N-terminal region of the circumsporozoite protein of Plasmodium berghei was attached to the distal end of di22:1-aminopropane-polyethyleneglycol(3400), and incorporated into liposomes containing di22:1-phosphatidylcholine and di22:1-phosphatidylethanolamine-polyethyleneglycol(5000). By systematically varying the mole fractions of both the lipid-polyethyleneglycol and the lipid-polyethyleneglycol-peptide conjugates, and screening for serum-induced aggregation in vitro, a serum-stable range of formulations was established.

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Previous studies demonstrated that intravenously administered liposomes, incorporating a peptide from the Plasmodium circumsporozoite protein, accumulate rapidly and selectively in mouse liver. The present investigation was designed to determine the molecular components in liver responsible for liposome targeting. Studies of liver tissue slices demonstrated that immunoreactivity for heparan sulfate proteoglycan (HSPG), but not other tested proteoglycans, was distributed along sinusoidal borders of liver; this immunoreactivity appeared associated with nonparenchymal cells of the sinusoids and with the basolateral portion of hepatocytes.

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Purpose: Several species of the protozoan Plasmodium effectively target mammalian liver during the initial phase of host invasion. The purpose of this study was to demonstrate that a Plasmodium targeting amino acid sequence can be engineered into therapeutic nanoparticle delivery systems.

Methods: A 19-amino peptide from the circumsporozoite protein of Plasmodium berghei was prepared containing the conserved region I as well as a consensus heparan sulfate proteoglycan binding sequence.

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Fluorescent proteins have emerged as an ideal fluorescent marker for studying cell morphologies in vital systems. These proteins were first applied in whole organisms with established germ-line transformation protocols, but now it is possible to label cells with fluorescent proteins in other organisms. Here we present two ways to introduce GFP expressing plasmids into avian embryos for vital confocal and two-photon imaging.

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