Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins.

N-myc expression is under stage- and tissue-specific regulation in mammalian development, but its function is totally unknown. We sought agents to block N-myc activity in order to infer from the effect the possible function of N-myc in the apparently complex processes. As candidates for such agents, we tested fusion genes encoding N-myc:beta-galactosidase fusion proteins for their effects on the formation of transformed foci of rat embryo primary fibroblasts as the result of transfection with N-myc and activated H-ras. One of the gene constructs very efficiently antagonized N-myc activity, as assessed by its effect on focus formation, but did not appreciably affect cell viability. The product of this gene was not only targeted to the nucleus but also accumulated in subnuclear loci which may represent the sites where normal N-myc proteins reside. The occurrence of antagonistic effect at a low stoichiometric ratio suggested that the fusion protein gene competed with the N-myc gene in a fashion analogous to a dominant negative mutation.     

Polysaccharide derivatives as coats for nylon tube urease

Urease was immobilized on O-alkylated nylon tubes coated with polyaminated derivatives of starch or dextran. The specific activity of the enzyme coil and the relative stability of the immobilized enzyme, compared with immobilized urease derived from other nylon tube modifications, were enhanced. Also, the nonspecific binding of urease to O-alkylated nylon tubes was virtually eliminated by the coating process.     

Role of virus inhibitory factor or interferon in the antitumoral effect of whole-body hyperthermia

The interferon inducing effect of hyperthermia was studied in normal and tumor-bearing mice. Circulating interferon was temporarily detected one day after subcutaneous transplantation of 1.6 X 10(6) Ehrlich's ascites tumor cells. Hyperthermia of 43.5 degrees C for 5 min did not induce the interferon formation in mice with or without subcutaneous tumor of the cells. These findings showed that the induction of interferon formation was not main cause of the hyperthermia-induced tumor inhibition.     

Fenestrated capillaries in the ventral sebaceous gland of the Djungarian hamster, Phodopus sungorus

The ventral sebaceous gland of the Djungarian hamster is a macroscopically visible organ situated in the midventral area of the abdominal wall. It consists of densely packed acini arranged in lobules with common excretory ducts. The rich vascular network of the gland is characterized by fenestrated capillaries. Fenestrated endothelium has not yet been reported as a characteristic and regular finding within sebaceous glands. Results are discussed with regard to proliferation rate of sebocytes and the demand of fluid and nutrient supply.     

Treatment of murine lupus with F(ab')2 fragments of monoclonal antibody to L3T4. Suppression of autoimmunity does not depend on T helper cell depletion

Treatment with mAb to the L3T4 Ag on Th cells can inhibit autoimmunity in mice. However, the mechanism by which anti-L3T4 inhibits autoimmunity is not known. In these studies, lupus-prone NZB/NZW F1 (B/W) mice were treated with F(ab')2 fragments of mAb to L3T4 to determine whether Th cell depletion is required for the beneficial effects of anti-L3T4. We first showed that treatment of female B/W mice with F(ab')2 anti-L3T4 from age 5 to 9 mo significantly reduced autoantibody production without depleting L3T4+ cells. However, treatment was complicated by the development of a host immune response to the rat mAb fragments. To circumvent this problem, female B/W mice were treated with a single high-dose of intact rat mAb to L3T4 (GK1.5) at age two mo. to induce immune tolerance to the mAb. Then, after recovery of L3T4+ cells, the mice were treated from age four to 14 mo with either F(ab')2 anti-L3T4 (0.5 mg 3 times per wk), intact anti-L3T4, or saline. In mice tolerized by this regimen, neither the F(ab')2 rat mAb nor the intact rat mAb elicited a host response. The mAb fragments bound target Ag but did not deplete the Th cells, whereas intact mAb to L3T4 profoundly depleted the L3T4+ cells. Despite this difference, both therapies had the same substantial beneficial effects on autoimmunity. They significantly decreased anti-DNA Ab production, improved renal function and prolonged survival. The initial tolerizing dose, by itself, did not inhibit autoimmunity. These findings show that anti-L3T4 suppresses autoimmunity by directly altering Th cell function through the L3T4 Ag, and not solely by depleting Th cells. They also document the detrimental effects of the host immune response to therapy with anti-L3T4 mAb, and they demonstrate a new strategy by which this response may be prevented.