A novel plasmal conjugate to glycerol and psychosine ("glyceroplasmalopsychosine"): isolation and characterization from bovine brain white matter.

A novel plasmal conjugate of glycosphingolipid having cationic lipid properties was isolated from the white matter of bovine brain. Linkage analysis of galactosyl residue by methylation, liquid secondary ion, and electrospray ionization mass spectrometry of intact and methylated derivatives, and by (1)H- and (13)C-NMR spectroscopy, identified the structure unambiguously as an O-acetal conjugate of plasmal to the primary hydroxyl group of glycerol and to the 6-hydroxyl group of galactosyl residue of beta-galactosyl 1-->1 sphingosine (psychosine). This novel compound is hereby termed "glyceroplasmalopsychosine"; its structure is shown below (see text).

A simple method for the synthesis of ceramides and radiolabeled analogues.

A simple method has been developed for the coupling of amines to carboxylic acids. N-Fatty-acyl-sphingosine, cerebroside, and GM3, as well as their respective [14C] analogues, were synthesized using diethylphosphoryl cyanide as a potent coupling agent in the presence of triethylamine. The reaction procedure is rapid, racemization-free, and utilizes acids without derivatization. The desired ceramide products were obtained in 85-90% yield within one hour. The facile method presented here can also be used to synthesize [3H]-N-acyl-labeled, as well as [14C] [3H] double-labeled, ceramides.

Plasmalopsychosine of human brain mimics the effect of nerve growth factor by activating its receptor kinase and mitogen-activated protein kinase in PC12 cells. Induction of neurite outgrowth and prevention of apoptosis.

Plasmalopsychosine, a characteristic fatty aldehyde conjugate of beta-galactosylsphingosine (psychosine) found in brain white matter, enhances p140trk (Trk A) phosphorylation and mitogen-activated protein kinase (MAPK) activity and as a consequence induces neurite outgrowth in PC12 cells. The effect of plasmalopsychosine on neurite outgrowth and its prolonged activation of MAPK was similar to that of nerve growth factor (NGF), and the effect was specific to neuronal cells. Plasmalopsychosine was not capable of competing with cold chase-stable, high affinity binding of NGF to Trk A, indicating that plasmalopsychosine and NGF differ in terms of Trk A-activating mechanism. Tyrosine kinase inhibitors K-252a and staurosporine, known to inhibit the neurotrophic effect of NGF, also inhibited these effects of plasmalopsychosine, suggesting that plasmalopsychosine and NGF share a common signaling cascade. Plasmalopsychosine prevents apoptosis of PC12 cells caused by serum deprivation, indicating that it has "neurotrophic factor-like" activity. Taken together, these findings indicate that plasmalopsychosine may play an important role in development and maintenance of the vertebrate nervous system.

Proximal femoral fractures: prevalence in different racial groups.

This paper describes the methodology and the results of a study performed in Central England. The predominant racial group here is "White European" (Europid). There are smaller numbers of people of Indian origin (Indids) and still smaller numbers of Afro-Caribbean and of Mongolian ancestry (Mongoloids). We found no significant differences in the incidence of hip fractures in the first two groups. The study population was 1600 consecutive patients with proximal femoral fractures (PFF). The difficulties of racial classification are discussed. To elucidate the predisposing factors for PFF, large scale collaborative studies between medical centres in the major European, Asian, African and American conurbations are suggested. Racial burden may be one such factor; osteoporosis may be another.