Comparison of calcium phosphate cement mixture and pure calcium hydroxide as direct pulp-capping agents

This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins.     

Determination of the total attenuation coefficient for six contact lens materials using the Beer-Lambert law

The Beer-Lambert law has been used to determine the total attenuation coefficient, mu t, of three hard and three soft contact lens materials. The three hard contact lens materials were PMMA, Polycon II and Boston IV whereas the 3 soft materials were chosen with differing water contents of 38, 55 and 70%, respectively. The total attenuation coefficients of all six materials were obtained from measurements of the axial transmission at 632.8 nm of a series of plano powered lenses varying in axial thickness from 0.5 to 3.5 mm. The value of the total attenuation coefficient depends on both scattering and absorption and hence PMMA and Boston IV, which both incorporated a handling tint, showed significantly higher values (P < 0.0001) of mu t (0.562 +/- 0.010 mm-1 and 0.820 +/- 0.008 mm-1, respectively) than Polycon II (mu t = 0.025 +/- 0.005 mm-1). A comparison between Polycon II and the three hydrated soft contact lens materials showed a significant increase (P < 0.02) in the total attenuation coefficients for the 38% and 55% water content materials, and a weakly significant increase for the 70% water content soft lens material (P < 0.1). On the assumption that the absorption coefficients of these four materials are approximately constant, then this change would be due to an increase in the scattering coefficient of the material and could contribute to an increase in intraocular scatter. No significant difference (P > 0.5) was found between any of the hydrated soft contact lens materials tested.     

Evidence for phosphorylation of CTP:phosphocholine cytidylyltransferase by multiple proline-directed protein kinases

Reversible phosphorylation of CTP:phosphocholine cytidylyltransferase, the rate-limiting enzyme of phosphatidylcholine biosynthesis, is thought to play a role in regulating its activity. In the present study, the hypothesis that proline-directed kinases play a major role in phosphorylating cytidylyltransferase is substantiated using a c-Ha-ras-transfected clone of the human keratinocyte cell line HaCaT. Cellular extracts from epidermal growth factor-stimulated HaCaT cells and from ras-transfected HaCaT cells phosphorylated cytidylyltransferase much stronger as compared with extracts from quiescent HaCaT cells. The tryptic phosphopeptide pattern of cytidylyltransferase phosphorylated by cell-free extracts from ras-transfected HaCaT cells was similar compared with the patterns of cytidylyltransferase phosphorylated by p44mpkmitogen-activated protein kinase and p34cdc2 kinase in vitro, whereas in the case of casein kinase II the pattern was different. Furthermore, in c-Ha-ras-transfected HaCaT cells the in vivo phosphorylation state of cytidylyltransferase was 2-fold higher as compared with untransfected HaCaT cells. This higher phosphorylation of cytidylyltransferase in the ras-transfected clone was reduced to a level below the phosphorylation of cytidylyltransferase in untransfected cells, using olomoucine, a specific inhibitor of proline-directed kinases. The reduced phosphorylation of cytidylyltransferase in olomoucine-treated cells correlated with an enhanced stimulation of enzyme activity by oleic acid.     

Transport of macromolecules through microvascular walls

This review addresses the long-standing controversy over the principal mechanisms of transport of macromolecules through the endothelium of microvessels of 'normal' permeability. Two types of mechanism have been proposed: convective transport through 'large pores' in the endothelium: transport via vesicles (transcytosis). The different techniques for estimating microvascular permeability to macromolecules are described and values for microvascular permeability to serum albumin in different tissues are tabulated. Whereas the evidence for convective transport when obtained from experiments on perfused microvascular beds remains convincing, attention is drawn to recent measurements using the tracer uptake technique which suggest that transport in the intact circulation from blood to tissues may not be coupled to fluid movement. Direct evidence for the involvement of endothelial vesicles in transendothelial transport has been reported relatively recently but the mechanisms whereby macromolecules are conveyed through the vesicular system have yet to be established. The possibility of convective transport through transient transendothelial channels formed by the fusion of vesicles is discussed.     

Specificity of the H-2 L(d)-restricted cytotoxic T-lymphocyte response to the mouse hepatitis virus nucleocapsid protein

Cytotoxic T lymphocytes provide protection against persistent infection of the central nervous system by the JHM strain of mouse hepatitis virus. In BALB/c (H-2d) mice, the dominant response is directed against an Ld-restricted peptide in the nucleocapsid protein (APTAGAFFF). Characterization of the fine specificity of this response revealed that the predicted anchor residues at positions 2 and 9 were the most critical for class I binding. Amino acids at positions 7 and 8 were identified as T-cell receptor contact residues. Virus-induced cytotoxic T lymphocytes to other Ld motif-containing nucleocapsid peptides were not detected, despite the identification of two epitopes with reduced Ld affinity. These data suggest that mutations within four residues of the dominant epitope could contribute to the persistence of the JHM strain of mouse hepatitis virus.     

Src tyrosine kinase activity is related to luteinizing hormone responsiveness: genetic manipulations using mouse MA10 Leydig cells

The Src family of tyrosine kinases play an important role in various signal transduction pathways in many different cell types, however, the role of these kinases in steroidogenic cells has not been examined. In the present study, genetic approaches were used to directly alter Src tyrosine kinase activity in mouse MA10 Leydig cells in order to determine the effect of changes of Src activity on LH-responsiveness with regard to cAMP and progesterone secretion. MA10 cells expressing a dominant negative Src (MA10(Srck-3)) secreted more cAMP and progesterone in response to LH than control transfected cells. Phosphodiesterase activity was decreased in MA10(Srck-3) cells. Conversely, MA10 cells expressing a temperature sensitive Src (MA10(tsUP)) lost LH-responsiveness with regard to cAMP and progesterone secretion at the Src active temperature (35 degrees C). It is concluded that Src tyrosine kinase has an important role in regulating steroid secretion in MA10 Leydig cells. This regulation may in part be due to Src modulation of phosphodiesterase activity, although other components of the LH-signaling pathway may be involved.     

Engineering epidermal growth factor for enhanced mitogenic potency

Successful use of growth factors in therapeutic and bioprocessing applications requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. Current ameliorative strategies use physiologically inappropriate high growth-factor concentrations, along with periodic media refeeding in vitro and reinjection or controlled-release devices in vivo. We demonstrate a new approach derived from understanding how these attenuation mechanisms arise from ligand/receptor trafficking processes. Specifically, a recombinant epidermal growth factor (EGF) mutant with reduced receptor binding affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or transforming growth factor alpha because of its altered trafficking properties.     

Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell activation

We have developed peptide analogs to analyze precise human CD4 substructures involved in MHC class II binding. Forms of the complementarity determining-like regions (CDRs) of the D1 domain of human CD4 were reproduced as synthetic aromatically modified exocyclic (AME) analogs and tested for their ability to block CD4-MHC II interactions and T cell activation. The exocyclic derived from CDR3 (residues 82-89) of human CD4, which specifically associated with CD4 on the T cell surface to create a heteromeric CD4 complex, blocked IL-2 production and antagonized the normal function of the CD4 receptor. The approach of creating novel synthetic antagonistic receptor complexes may represent a new receptor specific pharmaceutical approach to modulate biological function.