Type 2 diabetes is preceded by the development of insulin resistance, in which the action of insulin is impaired, largely in skeletal muscles. Caveolin-3 (Cav3) is a muscle-specific subtype of caveolin, an example of a scaffolding protein found within membranes. Cav is also known as growth signal inhibitor, although it was recently demonstrated that the genetic disruption of Cav3 did not augment growth in mice. We found, however, that the lack of Cav3 led to the development of insulin resistance, as exemplified by decreased glucose uptake in skeletal muscles, impaired glucose tolerance test performance, and increases in serum lipids. Such impairments were markedly augmented in the presence of streptozotocin, a pancreatic ␤ cell toxin, suggesting that the mice were susceptible to severe diabetes in the presence of an additional risk factor. Insulinstimulated activation of insulin receptors and downstream molecules, such as IRS-1 and Akt, was attenuated in the skeletal muscles of Cav3 null mice, but not in the liver, without affecting protein expression or subcellular localization. Genetic transfer of Cav3 by needle injection restored insulin signaling in skeletal muscles. Our findings suggest that Cav3 is an enhancer of insulin signaling in skeletal muscles but does not act as a scaffolding molecule for insulin receptors. Diabetes mellitus comprises a group of common metabolic disorders that share the phenotype of hyperglycemia (1). In particular, adult-onset diabetes, or type 2 diabetes, is a heterogeneous group of disorders usually characterized by varying degrees of insulin resistance and increased blood glucose concentrations. Insulin binding to insulin receptors (IR) evokes a cascade of phosphorylation events, as commonly seen in other growth factor signaling, beginning with the autophosphorylation of IR in multiple tyrosyl residues, followed by downstream signaling events (2). The combined actions of these events mediate the biological effects of insulin, leading to increased glucose uptake.Caveolin (Cav) is a major protein component of caveolae, flask-shaped plasma membrane invaginations found in myocytes, endothelial cells, fibroblasts, and adipocytes (for review, see ref.3). Numerous studies have indicated that Cav works as a scaffolding molecule; it binds directly to various receptors and their effector molecules and anchors these molecules to the caveolae. More important, Cav inhibits the function of these molecules. Cav-1 (Cav1)-mediated inhibition, by the use of a short stretch of the amino terminus domain of Cav (or the Cav scaffolding domain peptide), has been demonstrated with various kinases involved in cellular growth, such as receptor tyrosine kinases, e.g., epidermal growth factor-R (4) or platelet-derived growth factor-R (5), as well as protein kinase C (6) or Src (7). These studies have demonstrated that the Cav1 peptide directly bound to these molecules and inhibited their activity. Accordingly, it is now believed that Cav1 is an inhibitor of cellular growth signal (8-10).Cav3 is the newest...

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ClearLight performed eight times over 4 weeks can be useful in the treatment of acne. Further investigation will be needed to elucidate the mechanism of action of ClearLight.

We report on an 80-year-old man with rheumatoid arthritis (RA) who presented with chronic myelogenous leukemia (CML). Five years after the onset of RA, the CML diagnosis was made. The patient was treated for CML with 300 mg of imatinib mesylate (STI; signal transduction inhibitor 571) for 8 weeks. Laboratory tests showed that the C-reactive protein level, percentage of cells exhibiting the Philadelphia chromosome (Ph1), WBC count, and Lansbury index for RA all dropped respectively from 7.5 mg/dl to 1.0 mg/dl, 74.9% to 1%, 25, 100/microl to 9900/microl, and 51% to 14%. Administration of imatinib mesylate is felt to be effective in treating not only CML but also RA in the active stage.

The presence of the anti-68/48 kDa protein antibodies in a portion of both CFS and primary FM patients suggests the existence of a common immunological background. These antibodies may find utility as possible markers for a clinicoserological subset of CFS/FM patients with hypersomnia and cognitive complaints.

The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.

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SUMMARYWe have reported previously that p95c, a novel 95-kDa cytosolic protein, was the target of autoantibodies in sera of patients with autoimmune hepatic diseases. We studied 30 sera that were shown previously to immunoprecipitate a 95 kDa protein from [35 S]-methionine-labelled HeLa lysates and had a specific precipitin band in immunodiffusion. Thirteen sera were available to test the ability of p95c antibodies to inhibit nuclear envelope assembly in an in vitro assay in which confocal fluorescence microscopy was also used to identify the stages at which nuclear assembly was inhibited. The percentage inhibition of nuclear envelope assembly of the 13 sera ranged from 7% to 99% and nuclear envelope assembly and the swelling of nucleus was inhibited at several stages. The percentage inhibition of nuclear assembly was correlated with the titre of anti-p95c as determined by immunodiffusion. To confirm the identity of this autoantigen, we used a full-length cDNA of the p97/valosin-containing protein (VCP) to produce a radiolabelled recombinant protein that was then used in an immunoprecipitation (IP) assay. Our study demonstrated that 12 of the 13 (93%) human sera with antibodies to p95c immunoprecipitated recombinant p97/VCP. Because p95c and p97 have similar molecular masses and cell localization, and because the majority of sera bind recombinant p97/VCP and anti-p95c antibodies inhibit nuclear assembly, this is compelling evidence that p95c and p97/VCP are identical.