[The glucagonoma syndrome. 3 new cases]. / Le syndrome du glucagonome: trois nouveaux cas.

We report three new cases of glucagonoma revealed, 6 to 12 months after its onset, by non-specific and misleading skin lesions associated in all 3 cases with diabetes mellitus, severe deterioration of the general condition and hyperglucagonaemia. Non-invasive methods, such as ultrasonography and computerized tomography (CT), are most helpful to locate the pancreatic tumour. Phlebography with tiered venous blood sampling is useful in difficult cases. A false positive result has been recorded with arteriography. Ultrasonography and CT have yielded two false negative results. The alpha-chain of the chorionic gonadotrophin hormone has limited value in the diagnosis of malignant glucagonoma. Treatment is surgical, but despite it, the prognosis is severe (two of our three patients died), due to the risk of thromboembolism, to cachexia and to metastases that are frequent at the time of diagnosis.

Distribution of lipid synthesizing enzymes, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and myelin proteins in rat forebrain subfractions during development.

The distribution of UDP-galactose:ceramide galactosyltransferase (CGalT) was studied in subcellular fractions of rat forebrain during development using zonal centrifugation on linear gradients. Specialized subfractions: SN 1, a microsomal fraction, SN 4, a myelin-related fraction, and purified myelin were also used for this study. For comparison, two microsomal lipid synthesizing enzymes, a myelin-specific enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin proteins were measured in the same subfractions. UDP-glucose:ceramide glucosyltransferase and cerebroside sulfotransferase were confined to microsomes. CGalT was localized in microsomes, but also in myelin and myelin-related fractions. The developmental change in distribution of CGalT in adult animals toward myelin containing fractions could indicate that the replacement of galactosylceramide in compact myelin could be carried out in close proximity to compact myelin (mesaxon, paranodal loops) rather than in the distant oligodendrocyte perikaryon.

Lipid metabolism and oxygen consumption in a hereditary demyelinating neuropathy, the trembler mouse: an in vitro study.

Sciatic nerves from 15-day-old trembler and control mice were maintained in vitro up to 53 h and the metabolism of myelin lipids and the oxygen consumption were investigated [35S]Sulfate was incorporated into sulfatides at a higher rate and turned over more rapidly in trembler nerves than in controls. [14C]Galactose was incorporated into cerebrosides of trembler nerves at a lower rate and turned over like the controls. In contrast, synthesis of sulfatides labeled with [14]galactose was increased in mutants and no significant turnover was observed for both trembler and control nerves during the whole incubation period. Similar results were obtained using [3H]serine as a precursor and no significant differences were observed in the turnover rates of sphingomyelin and phosphatidylcholine between trembler and control nerves. These data suggest the presence of two different pools of cerebrosides, a small one formed by the fast recycling of sulfatides and which does not mix with a second, larger one. The rate of oxygen consumption did not change significantly during the incubation period and was 2-3-fold higher in trembler nerves than in controls, reflecting, at least partly, the increased sulfatide metabolism.

Myelin proteins, glycoproteins, and myelin-related enzymes in experimental demyelination of the rabbit optic nerve: sequence of events.

Wallerian degeneration of the rabbit optic nerve was investigated by the technique of retinal ablation which precludes edema, hemorrhage, or macrophage infiltration. After 8 days of degeneration, marked degradation of axons and some myelin abnormalities appeared in the optic nerve, optic chiasma, and optic tract. Myelin lesions were maximal 32 days after retinal destruction. The amount of material stained with a myelin dye decreased drastically between 32 and 90 days after the operation. Biochemical parameters gave the following sequence of events. The concentration of the major periodic acid--Schiff staining glycoproteins was decreased after 2 days, and 6 days later the presence of cholesterol esters was detected in the optic tissue. After 16 days of Wallerian degeneration, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase not associated with myelin decreased, indicating a possible de-differentiation of oligodendrocytes. Degradation of myelin basic protein became significant at 32 days and the amount of myelin isolated decreased later. The loss of myelin basic protein coincided with a reduction of myelin periodicity as measured in purified fractions by electron microscopy. These results show that secondary myelin destruction in the absence of edema, hemorrhage, or macrophages is a very slow process, and in this situation myelin undergoes a selective and sequential loss of its constituents.

Evidence for the association of 2',3'-cyclic-nucleotide 3'-phosphodiesterase with myelin-related membranes in peripheral nervous system.

In PNS, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in myelin was not enriched over the starting homogenate. Nevertheless, most of the total activity was recovered in myelin. In myelin-deficient mutants, low CNP activities were measured in sciatic nerves. CNP specific activities were similar in myelinated and non-myelinated nerves but in non-nervous tissues, they were significantly lower than in nervous tissue. There was no indication for the presence of an isoenzyme of CNP in peripheral nerves. These results indicate that CNP is present in PNS myelin and preferentially localized in Schwann cell plasma membranes.

Abnormal sulfate metabolism in a hereditary demyelinating neuropathy.

Trembler mice are affected by dominantly inherited neuropathy. Total lipid content and sulfatides were decreased in peripheral nerves from 15-day-old mutants. The proportion of sulfatides in per cent of total lipids was similar in control and Trembler nerves. The specific activity of ceramide galactosyltrnsferase, the enzyme responsible for the synthesis of cerebrosides, was 36 and 13% of controls, in young and adult. Trembler nerves, respectively. In contrast, cerebroside sulfotransferase activities were increased by 257 and 172% in young and adult Trembler sciatic nerves, respectively. No activator or inhibitor effect could be demonstrated. In Trembler PNS, Km, Vmax and heat sensitivity of CST differed from controls. Low levels of substrate and high arylsulfatase A activity (218% of controls) could explain the lack of sulfatide accumulation. The increased in vivo sulfate and galactose incorporation into non-lipidic material couild reflect the overproduction of endoneurial and perineurial connective tissue, whereas the high turnover rate of sulfatides could be correlated with intense demyelination and remyelination observed in Trembler PNS.