[Oral amyloidosis and multiple myeloma. Apropos of a case and review of the literature]. / Amyloïdose orale et myélome multiple. A propos d'un cas et revue de la littérature.

We describe a case of amyloidosis with oral involvement as a complication of multiple myeloma. Through a review of the literature, the classification, the pathogenesis, the epidemiological and clinical aspects, the prognosis, the diagnosis and medical treatment of amyloidosis are discussed.

A novel non-mineral oil-based adjuvant. I. Efficacy of a synthetic sulfolipopolysaccharide in a squalane-in-water emulsion in laboratory animals.

Sulfolipopolysaccharides (SLPs) were synthesized by reaction of the synthetic polysucrose polymer Ficoll-400 with chlorosulfonic acid and lauroyl chloride in anhydrous medium. Hydrophobic derivatives were obtained by addition of a small number of sulfate and a large number of lipid groups. Gel-permeation high-performance liquid chromatography (g.p.-h.p.l.c.) exhibited a wide range in molecular weight of both Ficoll-400 and SLP polymers. The calculated weight-average molecular weight (Mw) of Ficoll-400 and SLP using polystyrene polymers as references was 187,000 and 380,000 respectively, exhibiting a twofold increase in molecular weight upon derivatization. Adjuvanticity of hydrophobic SLPs with 0.2 sulfate and 1.5 lipid groups per sucrose monomer, a squalane-in-water emulsion (S/W), SLP incorporated into S/W (SLP/S/W), and a mineral oil-based emulsion (O/W) was investigated in combination with different antigens in mice and guinea-pigs. Antibody responses in serum against ovalbumin (OVA), dinitrophenylated bovine serum albumin (DNP-BSA), inactivated influenza virus strain MRC-11 (MRC-11), a mixture of three influenza virus strains (iFlu3) and inactivated pseudorabies virus (iPRV) were measured by either haemagglutination (HA), haemagglutination inhibition (HI) or serum neutralization (SN). Vaccines were prepared by simply mixing one volume of antigen with one volume of adjuvant solution. Antibody titres after one or two injections with these antigens were enhanced significantly by SLP/S/W, SLP, S/W and O/W and in most studies, SLP/S/W was demonstrated to be more effective than either the two constituent components or the O/W adjuvant.(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphate dependency of phosphofructokinase 2.

Experiments performed at micromolar concentrations of inorganic phosphate support the conclusion that liver phosphofructokinase 2 would be completely inactive in the absence of inorganic phosphate or arsenate. The concentration of inorganic phosphate that allowed half-maximal activity decreased with increasing pH, being approximately 0.11 mM at pH 6.5 and 0.05 mM at pH 8. The effect of phosphate was to increase V and to decrease Km for fructose 6-phosphate, without affecting Km for ATP. Citrate and P-enolpyruvate inhibited the enzyme non-competitively with fructose 6-phosphate and independently of the concentration of inorganic phosphate. Phosphorylation of the enzyme by the catalytic subunit of cyclic-AMP-dependent protein kinase did not markedly modify the phosphate requirement and its effect of inactivating phosphofructokinase 2 could not be counteracted by excess phosphate. A nearly complete phosphate dependency was also observed with phosphofructokinase 2 purified from Saccharomyces cerevisiae or from spinach leaves. By contrast, the fructose 2,6-bisphosphatase activity of the liver bifunctional enzyme was not dependent on the presence of inorganic phosphate. Phosphate increased this activity about threefold when measured in the absence of added fructose 6-phosphate and a half-maximal effect was reached at approximately 0.5 mM phosphate. Like glycerol phosphate, phosphate counteracted the inhibition of fructose 2,6-bisphosphatase by fructose 6-phosphate, but a much higher concentration of phosphate than of glycerol phosphate was required to reach this effect.

On the mechanism by which glucocorticoids cause the activation of glycogen synthase in mouse and rat livers.

The administration of glucocorticoids to mice caused within 3 h an inactivation of glycogen phosphorylase and activation of glycogen synthase in their livers. In a Sephadex filtrate of liver extract, as well as in a purified glycogen fraction obtained from treated mice, but not in the same preparations obtained from control mice, glycogen synthase was activated without previous inactivation of phosphorylase. The initial rate of synthase activation in a Sephadex filtrate was proportional to the rate of glycogen synthesis in vivo in the same animal. When the glycogen fraction was isolated in the presence of soluble starch, it could be separated from phosphorylase, phosphorylase phosphatase and synthase phosphatase. When added to a control Sephadex filtrate, this purified glycogen fraction obtained from prednisolone-treated mice relieved synthase phosphatase from inhibition by phosphorylase a, indicating that it contained a transferable 'deinhibiting factor'. This deinhibiting factor appears to be a protein and was further purified by alkyl-Sepharose or DEAE-cellulose chromatography. Another modification introduced by treatment with prednisolone was that phosphorylase phosphatase was 1.5-2-fold more active than in the liver of control mice. This property however did not correlate with the rate of glycogen synthesis in vivo. Administration of actinomycin D prevented the expression of the glucocorticoid effects on the rate of glycogen synthesis in vivo and on the protein phosphatases in vitro. The deinhibition of synthase phosphatase was also observed in isolated rat hepatocytes incubated in the presence of glucocorticoids, but in these preparations synthase was not activated.

Glucocorticoids and hepatic glycogen metabolism.

The steady accumulation of glycogen in fetal rat liver during the last fifth of gestation is elicited by a transient rise in the level of circulating corticosterone. One effect of glucocorticoids is to induce glycogen synthase. The actual deposition of glycogen, however, depends on the appearance of a small amount of glycogen synthase in the active, dephosphorylated form. Induction of glycogen synthase phosphatase by glucocorticoids may explain the latter crucial process. Insulin enhances further the rate of glycogen deposition. The effect of insulin requires a previous exposure of the fetal liver to glucocorticoids. It is exerted on the enzyme interconversion system and appears not to involve new protein synthesis. Administration of glucocorticoids to adult fed or fasted animals causes within 3 h an intensive deposition of glycogen in the liver. This phenomenon is ultimately explained by both an activation of glycogen synthase and an inactivation of glycogen phosphorylase. The latter process may be due to an enhanced activity of phosphorylase phosphatase, or possibly of phosphorylase kinase phosphatase. The activation of glycogen synthase is explained by an enhanced activity of glycogen synthase phosphatase. The latter enzyme is normally profoundly inhibited by phosphorylase a; glucocorticoids cause the appearance in the liver of a protein factor that decreases and eventually cancels this inhibitory effect of phosphorylase a. It remains to be established whether or not some part of the glucocorticoid effect on adult liver is mediated by insulin.

Native and latent forms of liver phosphorylase phosphatase. The non-identity of native phosphorylase phosphatase and synthase phosphatase.

The directly measurable (native) phosphorylase phosphatase present in a fresh mouse liver extract is bound to particulate glycogen and is not inhibited by heat-stable inhibitors. Treatment of the extract with trypsin or ethanol at room temperature caused a more than 10-fold increase in phosphorylase phosphatase activity. This increased activity stems from the activation of completely inactive (latent) enzyme, the major part of which is present in the high-speed supernatant. The trypsin-revealed activity can be completely blocked by heat-stable inhibitors. Treatment of the animal with glucocorticoids increases, and fasting decreases the activity of the native phosphorylase phosphatase. The level of latent enzyme, however, is unaffected by these treatments. The major portion of synthase phosphatase in the fresh liver extract is bound to glycogen. This enzyme is inhibited by the heat-stable inhibitor-2 and inactivated by trypsin or ethanol as well as by several treatments that have little effect on phosphorylase phosphatase. Upon DEAE-cellulose chromatography at 0 degrees C of a fresh liver extract, phosphorylase phosphatase and synthase phosphatase were resolved as separate, single peaks. If the preparation was not kept at 0 degrees C during the entire procedure, two peaks of each enzyme were observed. Under these conditions the first peak of phosphorylase phosphatase and of synthase phosphatase coincided. From these findings it is concluded that synthase phosphatase and phosphorylase phosphatase, in their native form, are distinct enzymes.