Phorbol ester receptors in cerebral cortex of cats with GM1 gangliosidosis

The pathogenesis of neuronal dysfunction in the gangliosidoses is poorly understood. Studies of the feline gangliosidoses and in vitro experiments implicate ganglioside inhibition of protein kinase C (PKC) in the pathogenesis of these neurological diseases. Therefore, in the present study, the binding of [³H]phorbol-12, 13 dibutyrate was measured to determine the levels of PKC in cerebral cortex of cats with GM₁ gangliosidosis (mutant) and age matched normal siblings. This binding of ([³H]PDB) to cerebral cortex homogenates in both normal and mutant cats was highly specific. The specificity of receptors was ascertained also from displacement studies using nonradioactive phorbol ester analogues to displace [³H]PDB bound to its receptors. In both mutant and normal cat brain, phorbol 12, 13-dibutyrate (PDB), 4--phorbol 12,13-didecanoate (-PDA) and 4--phorbol 12,13-dibenzoate (-PDBz) were highly potent (approximately to same degree) and effective in displacing [³H]PDB. On the other hand, 4- phorbol 12,13-diacetate (-PDA) was a weak displacer and 4--phorbol did not displace the bound [³H]PDB in either normal or mutant brain. Scatchard analysis of the binding data indicated a homogenous single class of binding sites in normal and mutant brain (Normal: K_d=1.42×10^–7 M, B_max=8.40 pmoles/mg protein. Mutant: K_d=1.60×10^–7 M, B_max=10.00 pmoles/mg protein). Sphingosine inhibited the binding to approximately the same extent in normal and mutant cortex. These studies demonstrate the presence of highly specific, homogenous, single type phorbol ester receptors in cerebral cortex of cats with GM₁ gangliosidosis which are qualitatively and quantitatively similar to normal cat brain.     

Established cell lines from nonmammalian vertebrates: Models for DNA repair studies

Summary Several established cell lines from different classes of vertebrates were assayed for the presence of O⁶-methylguanine acceptor protein. This protein is instrumental in removing adducts from DNA caused by exposure to alkylating agents. Cultured cells had levels of acceptor protein activity within the range found in fresh tissues from animals in the same class. We suggest that cells from lower vertebrates are satisfactory in vitro models for studies of this DNA repair function.     

A comparison of the translational diffusion of a normal and a membrane-spanning lipid in Lα phase 1-palmitoyl-2-oleoylphosphatidylcholine bilayers

We have used the fluorescence recovery after photobleaching technique to study the translational diffusion, in L phase multibilayers of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), of fluorescent derivatives of 1-palmitoyl-2-oleoylphosphatidylethanolamine (NBD-POPE) and a membrane-spanning phosphatidylethanolamine (NBD-MSPE). The latter derivative was prepared from a membrane-spanning glycerol-dialkyl-glycerol tetraether lipid isolated from the thermophilic and acidophilic archaebacterium Sulfolobus solfataricus. The translational diffusion was examined between about 15° and 45°C. It is shown that over this temperature range the translational diffusion coefficient for NBD-MSPE is 2/3 that for NBD-POPE which spans only one monolayer of the bilayer. The result is interpreted in terms of existing models for translational diffusion in lipid membranes.Abbreviations D _t translational diffusion coefficient - FRAP fluorescence recovery after photobleaching - MSPE a membrane-spanning phosphatidylethanolamine derived from a glycerol-dialkyl-glycerol tetraether lipid isolated from Sulfolobus solfataricus - NBD 4-nitrobenz-2-oxa-1,3-diazolyl - PE phosphatidylethanolamine - POPC 1-palmitoyl-2-oleoylphosphatidylcholine - POPE 1-palmitoyl-2-oleoylphosphatidylethanolamine     

Stability in cyclic epidemic models

A general formulation for a family of cyclic epidemic models with density-dependent feedback mechanisms and removed classes is presented. A parameter, , related to the basic reproductive rate determines the asymptotic behaviour of solutions of the model. It is shown that if <1 the trivial solution is globally stable, and if >1 it is conditionally stable. The results are applied to a set of differential equations that has been used to model the life cycle of a parasite that has two hosts.     

General method for the derivation and numerical solution of epithelial transport models

Summary A general method is presented for the formulation and numerical evaluation of mathematical models describing epithelial transport. The method is based on the principles of conservation of mass, and maintenance of electroneutrality within the cells and bathing solutions. It is therefore independent of the specific membrane transport mechanisms, and can be used to evaluate different models describing arbitrary transport processes (including passive, active and cotransport processes). Detailed numerical methods are presented that allow computation of steady-state and transient responses under open-circuit, current-clamp and voltage-clamp conditions, using a general-purpose laboratory minicomputer. To evaluate the utility of this approach, a specific model is presented that is consistent with the Koefoed-Johnson and Ussing hypothesis of sodium transport in tight epithelia (Acta Physiol. Scand. 42:298–308, 1958). This model considers passive transport of an arbitrary number of permeant solutes, active transport of sodium and potassium, and osmotically induced water transport across the apical and basolateral membranes. Results of the model are compared to published experimental measurements in rabbit urinary bladder epithelium.     

Models for age structured populations with distributed maturation rates

In the use of age structured population models for agricultural applications such as the modeling of crop-pest interactions it is often essential that the model take into account the distribution in maturation rates present in some or all of the populations. The traditional method for incorporating distributed maturation rates into crop and pest models has been the so-called distributed delay method. In this paper we review the application of the distributed delay formalism to the McKendrick equation of an age structured population. We discuss the mathematical properties of the system of ordinary differential equations arising out of the distributed delay formalism. We then discuss an alternative method involving modification of the Leslie matrix.