A model for ganglioside behaviour in cell membranes

Gangliosides from beef brain have been spin-labeled using two different attaching groups and employed to investigate the physical nature of ganglioside behaviour in membranes. Results obtained using EPR spectroscopy indicate that, in phosphatidylcholine bilayers at physiological pH, ganglioside oligosaccharide chains are quite mobile and show a measurable tendency towards cooperative interaction amongst themselves. We suggest that the source of this interaction is the formation of H-bonds between sugar residues in adjacent ganglioside molecules. We present evidence that physiological (extracellular fluid) levels of Ca²⁺ and Mg²⁺ lead to cross-linking and condensing of ganglioside headgroups by complexing sialic acid carboxyl residues. Ganglioside headgroup interactions are not very sensitive to changes in the buffer ionic strength, suggesting that ionic interactions are of minor importance. We have found no measurable tendency for headgroup carbohydrate to penetrate hydrophobic regions of lipid bilayers. EPR spectroscopy was also used to follow the interaction of spin-labeled gangliosides with the glycoprotein, glycophorin, and with intact BHK cells.We suggest that these carbohydrate-based interactions should contribute significantly to the properties of the eucaryotic cell glycocalyx. We predict that laterally mobile carbohydrate-bearing components of cell surfaces will show a tendency to cluster about complex glycoprotein arrays, especially if the species involved bear accessible carboxylic acid functions.     

Stability of an age specific population with density dependent fertility

A nonlinear version of the Lotka-Sharpe model of population growth is considered in which the age specific fertility is a function of the population size. The stability of an equilibrium population distribution is investigated with respect to both global and local perturbations. Sufficient conditions for such stability are presented, as are estimates for the rate of return of the population to the equilibrium configuration. Particular attention is paid to those situations in which the age dependent stability criteria coincide with those of age independent models.     

Hypoxanthine-guanine phosphoribosyl transferase deficiency

Summary In man congenital lack of an enzyme of the purine salvage system, hypoxanthineguanine phosphoribosyl transferase (HG-PRT E.C. 2.4.2.8), is mostly accompanied by a picture known as the Lesch-Nyhan syndrome. The degree of deficiency may vary from zero to a few percent of normal activity but a correlation between the severity of HG-PRT deficiency and the clinical picture has not been observed, no more than a correlation between HG-PRT deficiency and neurological dysfunction. But individuals with undetectable HG-PRT activity but without the Lesch-Nyhan syndrome have been described. Patients with partial HG-PRT deficiency have clinically distinctive findings. Sometimes mild neurological abnormalities are observed. Because of marked overproduction of uric acid severe gouty arthritis and renal dysfunction are often encountered in both complete and partial deficiency.There is considerable molecular heterogeneity in HG-PRT deficiency in man. Mutant enzymes may exhibit different kinetic and electrophoretic properties, indicating that there might be a mutation on the structural gene coding for HG-PRT.Lack of HG-PRT disturbs purine interconversions profoundly. In addition to an important function of HG-PRT in the uptake of the purine bases hypoxanthine and guanine into the cell, the effective uptake of inosine, guanosine and adenosine also seems to be dependent on HG-PRT. Uptake of purine bases into intact red blood cells occurs according to a two component mechanism, one component probably involving a phosphoribosyl transferase system.The inheritance of HG-PRT deficiency is X-linked recessive and it is transmitted by asymptomatic carrier females. Several methods have been introduced for carrier detection. As a consequence of X chromosome inactivation, in these females a mosaicism of HG-PRT positive and HG-PRT negative fibroblasts can be demonstrated after cloning or after selection of HG-PRT negative cells in a selective medium. A more rapid method involves direct measurements of HG-PRT activities in single hair roots from the scalp. Because hair roots develop more or less clonally, in heterozygote females HG-PRT positive and negative hair roots are encountered. HG-PRT deficiency can be detected antenatally by demonstrating the presence or absence of enzyme activity in ammiotic fluid derived fibroblasts qualitatively by autoradiography and quantitatively by ultramicrochemical measurements of enzyme activities in single or small numbers of cells.In studies with isolated cells the metabolic defect can be corrected in several ways. Metabolic cooperation between HG-PRT positive and HG-PRT negative cells leads to apparently normal phenotype of all cells, provided there is cell to cell contact. There is evidence that a missing enzyme product or a derivative might be transferred from the normal to the mutant cells. Apparent correction of the enzyme defect is also observed when HG-PRT deficient lymphocytes are stimulated with phytohaemagglutinin.The first data suggestive of genetic complementation between two human HG-PRT deficient cell strains by which hybrid cells can synthesize a functionally active HG-PRT, are consistent with the view that HG-PRT deficiency in man is due to a structural gene mutation. Recent results show that other interesting findings might come from experiments in which HG-PRT deficient cells are treated with exogenous genetic material (isolated DNA or metaphase chromosomes) to reactivate or induce HG-PRT activity.Supported by grants from FUNGO (Foundation for Medical Scientific Research in the Netherlands) and the Medical Prevention Fund.     

Stochastic processes in particle-number fluctuations in an electron-photon shower

The paper is concerned with the existence and asymptotic character of the nonlinear boundary value problemdG/dt=F(t,G,F, ¦α?β¦) (1) ¦α?β¦dF/dt=g(t,G,F, ¦α?β¦)G(o,¦α?β¦)=k ₁,G(∞,¦α?β¦)=k ₂ (2) as ¦α?β¦→ o+ The discussion is related to the problem of particle-number fluctuations in the theory of cosmic radiation andG andF denote respectively the probability generating functions for the electron distribution in an electron-initiated and a photon-initiated shower. A solution of the system (1) satisfying the boundary conditions (2) is constructed so that specified limiting conditions are fulfilled.     

The dermatoglyphics of American Negroes

Digital and palmar dermatoglyphics of 184 male and 224 female normal American Negroes were evaluated for digital patterns, digital ridge counts, palmar patterns, palmar main line terminations, accessory triradii and palmar creases. All subjects were seven year olds examined and found free of chronic or other genetic diseases. The results were presented for the left and right hand for the most part comparable to those of the African and other American Negro groups reported earlier. The distributions of the various dermatoglyphic features among the Negroes taken as a group were compared to those of the other racial groups and their differences were discussed.     

Nicotinic Receptor-Mediated Release of Noradrenaline in the Human Neuroblastoma SH-SY5Y

Abstract: Dimethylphenylpiperazinium iodide (a nicotinic agonist) evokes noradrenaline release from human neuroblastoma SH-SY5Y cells that have been pretreated with 12- O -tetradecanoylphorbol 13-acetate for 8 min. This effect of dimethylphenylpiperazinium iodide was inhibited by 1 μ M mecamylamine but not by 1 μ M atropine, which suggests that SH-SY5Y cells express nicotinic receptors coupled to the release of noradrenaline. Dimethylphenylpiperazinium iodide-evoked release was enhanced by 5 μ M Bay K 8644 (an L-type calcium agonist) and inhibited by 1 μ M nifedipine. Dimethylphenylpiperazinium iodide depolarised SH-SY5Y cells and enhanced the level of intracellular calcium in cells loaded with fura 2. The effects of dimethylphenylpiperazinium iodide on noradrenaline release, depolarisation, and intracellular calcium levels were all inhibited by 1 μ M desmethylimipramine. The results of this study show that nicotinic receptors in SH-SY5Y cells stimulate noradrenaline release by activation of L-type calcium channels.